Cucurbiturils and method for synthesis

ABSTRACT

A method for producing cucurbit[n]urils, where n is from 4 to 12, comprising mixing substituted and/or unsubstituted glycoluril with an acid and a compound that can form methylene bridges between glycoluril units, and heating the mixture to a temperature of from 20° to 120° to thereby form cucurbit[n]. Novel cucurbit[n]urils, where n=4, 5, 7, 8, 9, 10, 11 and 12 and substituted cucurbit[s,u]urils, where s=number of substituted glycoluril units, u=number of unsubstituted units and s+u=4-12 are also described.

The present invention relates to a method for preparing cucurbit[n]urilsand cucurbit[s,u]urils. The present invention also relates tocucurbit[n]urils, to cucurbit[s,u]urils, and to a method of separatingcucurbit[n]urils and/or cucurbit[s,u]urils. The present invention alsorelates to novel compounds used in the preparation of cucurbit[n]urilsand cucurbit[s,u]urils.

Cucurbituril is the name given to a cyclic oligomer formed by linkingsix (6) glycoluril units via methylene bridges. Cucurbituril was firstdescribed in the literature in 1905 in a paper by R. Behrend, E. Meyerand F. Rusche, Leibigs Ann; Chem.; 339, 1, 1905. The macrocyclicstructure of cucurbituril was first described in 1981 by W. A. Freemanet. al., “Cucurbituril”, J. Am. Chem. Soc., 103 (1981). 7367-7368.Cucurbituril has a chemical formula of C₃₆H₃₆N₂₄O₁₂ and is a macrocycliccompound having a central cavity. An AM1 minimised structure ofcucurbituril is shown in FIG. 1.

The internal cavity of cucurbituril has a diameter of about 550 pm, adepth of 650 pm with portals at either end about 400 pm across. Thisrigid cavity has been shown to have high selectively in binding avariety of medium-small molecules and in this regard reference is madeto Cintas. P. J. Inclusion Phenomena and Molecular Recognition inChemistry; 17, 205, 1994.

The preparation of cucurbituril has generally followed the procedurefirst described in the article by R. Behrend et. al. published in 1905.

In German patent no. DE 196 03377. published 7 Aug. 1997, a process forsynthesising cucurbituril is described. This process includes dissolvingacetylene diurea (glycoluril) in an aqueous solution of a strong mineralacid in the presence of excess formaldehyde, with warming. The water isevaporated from the mixture to completely eliminate the water from themixture. The remaining polymer mixture is then heated to a temperatureup to 145° C. to complete the reaction. The applicants for this patenthave stated that a yield of up to 82.4% of the theoretical yield can beobtained.

In German patent no. DE 4001139, the use of cucurbituril to removeorganic compounds with hydrophobic groups, dyes, decomposition productsfrom dyes and/or heavy metals from aqueous solutions is described. Thepatent actually states that a cyclic oligomer which is obtained bycondensation of urea, thiourea, derivates of urea and/or derivatives ofthe thiourea with dialdehydes and formaldehyde is used. Although thepatent states that the degree of polymerisation, n, of the cyclicoligomer varies between about 3 and about 8, the examples of the patentshowing cyclic oligomers having a degree of polymerisation, n, only of6. Example 1 shows the preparation of cucurbituril by heating glycolurilunder reflux with formaldehyde.

Experiments conducted by the present inventors in following theprocedure of Example 1 of DE 4001139 have shown that cucurbituril having6 glycoluril units joined together is formed. In the words of DE4001139, n=6 for this product. No evidence was found of any cyclicoligomer having a degree of polymerisation, n, other than 6. Indeed, apaper by Buschmann et. al., Inorgica Chimica Acta, 1992, 193.93 statesthat under the synthetic conditions as described in DE 400 1139, onlycucurbituril having a degree of polymerisation, n, of 6 is formed.

The present inventors have now developed a method for producingcucurbiturils having a degree of polymerization of 4 to 12. To assist indifferentiating such compounds, the present inventors have adopted theterminology “cucurbit[n]uril” where n is a number from 4 to 12, todenote the different compounds. For example, a cyclic oligomer having 4basic glycoluril (substituted or unsubstituted) units joined togetherwould be denoted as “cucurbit[4]uril”.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an AM1 minimized structure of unsubstitutedcucurbit[6]uril.

FIGS. 1a, 1 b, 1 c and 1 d show a scheme for the proposed reactionmechanism for the synthesis of cucurbit[n]urils from substituted and/orunsubstituted glycoluril.

FIG. 2 shows the minimized chemical structure of unsubstitutedcucurbit[4]uril prepared using PCT-Spartan.

FIG. 3 shows the minimized chemical structure of unsubstitutedcucurbit[5]uril prepared using PCT-Spartan.

FIG. 4 shows the minimized chemical structure of unsubstitutedcucurbit[7]uril prepared using PCT-Spartan.

FIG. 5 shows the minimized chemical structure of unsubstitutedcucurbit[8]uril prepared using PCT-Spartan.

FIG. 5a shows models of the structure of unsubstituted curcurbit[5]uril,unsubstituted cucurbit[8]uril and unsubstituted cucurbit[10]uril asestablished by analysis of the X-ray crystal structure. Formula 12 is amodel of the structure of unsubstituted cucurbit[5]uril, formula 13 is amodel of the structure of unsubstituted cucurbit[8]uril and formula 14is model of the structure of unsubstituted cucurbit[10]uril.

FIG. 6 is a graphical representation of the chemical shift of C¹³ NMRresonances for the methine C for the unsubstituted cucurbit[6]uril,cucurbit[7]uril, cucurbit[8]uril and cucurbit[10uril, and the predictedvalues for unsubstituted cucurbit[9]uril, cucurbit[11]uril,cucurbit[11]uril, cucurbit[12]uril and cucurbit[13]uril.

FIG. 7 is a graphical representation of the chemical shift of C¹³ NMRresonances for the methylene C for the unsubstituted cucurbit[6]uril,cucurbit[7]uril, cucurbit[8]uril and cucurbit[10uril, and the predictedvalues for unsubstituted cucurbit[9]uril, cucurbit[11]uril,cucurbit[11]uril, cucurbit[12]uril and cucurbit[13]uril.

In a first aspect, the present invention provides a method for producingcucurbit[n]urils, where n is from 4 to 12, comprising mixing substitutedand/or unsubstituted glycoluril with an acid and a compound that canform methylene bridges between glycoluril units, and heating the mixtureto a temperature of from 20° C. to 120° C. to thereby formcucurbit[n]urils. Preferably, n is from 5 to 10.

Preferably, the method of the present invention further comprises addinga salt to the mixture. It has been found that adding a salt to themixture assists in achieving the synthesis of a variety ofcucurbit[n]urils of differing unit sizes. Without wishing to be bound bytheory, it is believed that an ion templating effect may be occurring.Thus, selection of the particular salt can control the amount of aderived cucurbit[n]uril in the product.

It has also been found that a number of other compounds can be added tothe mixture in place of the salt, or in combination with the salt, toachieve the templating effect described above. The templating effectcauses the relative amount of cucurbit[n]urils of differing unit sizesto be altered if the salt or other compound is added to the mixture. Forexample, the salt or other compound, when added to the reaction mixture,may alter, the ratio of, say, cucurbit[5]uril to cucurbit[6]uril, whenthat ratio is compared with the ratio of cucurbit[5]uril tocucurbit[6]uril that is produced using reaction mixtures having no saltor other compound added thereto but otherwise reacted under identicalconditions.

For ease of description, such salts and other compounds will bedescribed hereinafter throughout this specification as “templatingcompounds”. In a preferred embodiment the method of the first aspect ofthe present invention further comprises adding one or more templatingcompounds to the mixture.

The templating compounds can be selected from a large number ofcompounds and indeed any compound that can alter the ratio ofcucurbit[n]urils of different unit sizes produced in the method of thepresent invention can be used as a templating compound. The templatingcompound may be an organic compound, a salt of an organic compound, oran inorganic compound. Suitable compounds that may be used as atemplating compound include ammonium chloride, lithium chloride, sodiumchloride, potassium chloride, rubidium chloride, caesium chloride,ammonium chloride, lithium bromide, sodium bromide, potassium bromide,rubidium bromide, caesium bromide, lithium iodide, sodium iodide,potassium iodide, rubidium iodide, caesium iodide, potassium sulfate,lithium sulfate, tetrabutylammonium chloride, tetraethylammoniumchloride, o-carborane, thioacetamide, N-(1-napthyl)ethylenediamine,2,2′-biquinoline, p-bromoaniline, taurine, blue tetrazolium,2-amino-3-methyl benzoic acid, indol-3-aldehyde, cysteine,4-acetamidoaniline, p-aminophenol, acetamide, 4-aminoacetophenone,4-dimethylaminobenzaldehyde, 2-aminobenzimidazole,bis-(4,4′-bipyridyl))-α,α′-p-xylene, red phosphorus, and lithiump-toluenesulfonate. The present inventors believe that a large number ofother compounds could be suitable for use as templating compounds andtherefore the above list should not be considered to be exhaustive. Theanions of the acid may also be considered to be a template.

The templating compounds may be added singly to the reaction mixture ortwo or more templating compounds may be added to the reaction mixture.

If a salt is used as the templating compound salt that is added to themixture is preferably a metal halide, ammonium halide, or thecorresponding sulphates, or metal tosylates. It is preferred that theanion of the salt corresponds to the anion of the acid used. Forexample, where the acid used is hydrochloric acid, a metal chloride orammonium chloride is the preferred salt. If sulphuric acid is used,metal sulphate or ammonium sulphate is the preferred salt. Similarly,iodide-containing salts are preferably used where hydriodic acid is theacid, and bromide-containing salts are preferably used where hydrobromicacid is used.

The acid is preferably a strong mineral acid or a strong organic acid.In principle, any acid can be used. The acid acts to catalyse thereactions taking place.

Preferred acids for use in the method of the first aspect of the presentinvention include sulfuric acid, hydrochloric acid, hydrobromic acid,hydroiodic acid, deuterated sulfuric acid, phosphoric acid,p-toluenesulfonic acid, and methane sulfonic acid. It will beappreciated that this list is not exhaustive and that any acid that cancatalyse the reaction may be used in the method of the first aspect ofthe present invention.

It is especially preferred that the acid has a concentration of at least5 M.

In some embodiments of the first aspect of the present invention, asolvent may also be added to the reaction mixture. The solvent ispreferably selected from trifluoroacetic acid, methanesulfonic acid and1,1,1-trifluorethanol.

The compound that can form methlene bridges between glycoluril units ismost preferably formaldehyde, paraformaldehyde, trioxane or one or moreprecursors for formaldehyde. For convenience, the invention willhereinafter be described with reference to the case where formaldehydeis used.

The mixture is preferably heated to temperature of from 20° C. to 110°C. more preferably 60° C. to 110° C. most preferably from 80° C. to 110°C. It is preferred that boiling of the mixture is avoided. Heating underreflux, as required in the prior art, is not required (but may be used).Such temperature conditions are much milder than those utilised in theprior art synthesis process that led to the formation ofcucurbit[6]uril. The prior art processes involved heating the mixtureunder reflux followed by heating to temperatures of up to 145 to 165° C.At room temperatures the present inventors have found that,cucurbit[n]uril was formed only if concentrated sulphuric acid w as usedas the acid. It has been found that the mixture should generally heheated to a temperature of 60° C. and above to produce cucurbit[n]urils,with increased yields being obtained at temperatures on the range of 80°C. to 100° C.

The glycolurils that are used in the present invention have anunsubstituted structure as shown in formula 1 below:

The general structure for the cucurbit[n]urils synthesised in accordancewith the process of the present invention is shown in formula 2 below:

wherein n=4 to 12, preferably 4 to 10.

Substituted and unsubstituted glycolurils, or a mixture thereof, may beused to synthesise cucurbit[n]uril in accordance with the presentinvention. Substituted glycolurils have the general formula as shown informula 3 below:

wherein R₁ and R₂ are the same or different and selected from anoptionally substituted straight chain, branched or cyclic, saturated orunsaturated hydrocarbon radical or R₁ and R₂form a cyclic hydrocarbonradical. The hydrocarbon radical for substituents R₁ and R₂ may includealkyl, alkenyl, alkynyl, aryl and heterocyclyl radicals. There are largenumbers of substituted glycolurils known in the literature. Particularreference is made to a review article by Harro Petersen in Synthesis,1973, 243-293, which contains a list of about 30 substitutedglycolurils. The entire contents of this review article are herebyexpressly incorporated into this specification by cross reference. Theliterature since the Petersen article has disclosed several otherexamples of substituted glycolurils and it is believed that essentiallyany α- or β-diketone could be used to make a glycoluril.

Investigations conducted by present inventors have shown thatcucurbit[n]uril-like systems can be synthesised with many of thesubstituted glycolurils, preferably when used in comjuntion withunsubstituted glycolurils. The following substituted glycolurilcompounds have been prepared adn used to synthesise substitutedcucurbit[n]urils:

The compounds of formulae 5, 6 and 7 above are novel and accordingly, inanother aspect, the present invention provides a substituted glycolurilcompound of formula 5, formula 6 or formula 7.

The synthesis of substituted cucurbit[n]urils opens the possibility ofbeing able to chemically link the substituted cucurbit[n]uril to asubstrate or to chemisorb them onto a substrate. The solubilitycharacteristics of the product may also be manipulated by selection ofappropriate substituents.

As mentioned earlier, cucurbit[6]uril was first characterised andsynthesised in 1905. However, the present inventors believe thatcucurbit[n]uril, where n=4, 5, 7, 8, 9, 10, 11 or 12 has neverpreviously been synthesised. Accordingly, in a further aspect, thepresent invention provides cucurbit[n]uril, where n=4, 5, 7, 8, 9, 10,11 or 12. Preferably, n=5, 7, 8, 9 or 10.

The present also provides substituted cucurbit[n]urils, where n=4, 5, 6,7, 8, 9, 10, 11 or 12. In order to clarify nomenclature when substitutedcucurbiturils are formed, the present inventors have proposed thatsubstituted cucurbiturils in accordance with the present invention beidentified by the scheme “cucurbit[s,u]uril”, where s=the number ofsubstituted glycoluril units and u=the number of unsubstitutedglycoluril units in the cucurbituril. Using this nomenclature, thepresent invention also provides cucurbit[s,u]uril, where s and u are asdefined above and s+u=4 to 12, preferably 5 to 10.

In all of the experimental work conducted by the present inventors todate in relation to substituted cucurbiturils, the substitutedcucurbiturils have incorporated both substituted and unsubstitutedglycoluril units into the cucurbituril structure. Thus, it is preferredthat u does not equal zero. If s equals zero, cucurbit[s,u]uril isequivalent to cucurbit[n]urils.

The substituted cucurbit[n]urils are preferably synthesized fromsubstituted glycoluril or a mixture of substituted and unsubstitutedglycoluril. The substituents may be as described above.

In order to show the structure of cucurbit[n]uril in cases where n=4, 5,7 or 8, minimised chemical structures were prepared using PC-Spartan, amolecular modelling and visualisation package. The minimised structuresare shown as formulae 8 to 11 in FIGS. 2 to 5:

The minimised structures of Formulae 8 to 11 clearly show the innercavity of the cucurbituril. As the value of n increases, the size of theinner cavity increases, which enables different compounds to fit intothe inner cavity.

The reaction product of the process of the present invention contains amixture of different cucurbit[n]urils or cucurbit[s,u]urils. There areseveral methods that could be used to separate and purify these productsand these are described below:

Successive Recrystallisation

All of the cucurbit[n]urils that have been observed are apparentlysoluble in acid solutions. Cucurbit[5 or 7 or 8 or 10]uril have beenpurified by successive recrystallisations from acid solutions. Becauseof the similar nature of the cucurbiturils, this is a slow process withmore than 10 recrystallisations required to purify cucurbit[7]uril. Asshown in the German patents cucurbit[6]uril can be obtained in arelatively pure state from a single recystallisation process.

Selective Dissolution/precipitation

We have been able to demonstrate that different cucurbiturils havemarkedly different solubilities in various salt solutions. It ispossible to separate cucurbit[6]uril and cucurbit[7]uril from a mixturecontaining cucurbit[5-8]urils by dissolving cucurbit[6 or 7]uril out ofthe complex mixture using a 0.1M Na₂SO₄ solution.

We have also demonstrated the use of selective precipitation as apurification method. A solution of cucurbit[6]uril and cucurbit[7]urilwas mixed with bis(4,4′-dipyridyl)-α,α′-p-xylene. ¹H NMR showed adecrease in signal due to the cucurbit[7]uril andbis(4,4′-dipyridyl)-α,α′-p-xylene with several crystals depositing outof the sample.

According to another aspect, the present invention comprises separatinga mixture of cucurbit[n]urils, where n=4 to 12, by mixing the mixture ofcucurbit[n]urils with a salt solution in which at least one of thecucurbit[n]urils, but not all of the cucurbit[n]urils, dissolves andseparating solids from the solution. Preferably, the method furthercomprising recovering at least one of the dissolved at least onecucurbit[n]urils from the solution. This method may also be used toseparate mixtures of different substituted cucurbit[s,u]urils.

As an example, lithium chloride in hydrochloric acid solutionsselectively assists the crystallisation of cucurbit[6]uril andcucurbit[8]uril leaving cucurbit[5]uril and cucurbit[7]uril in solution.

Potassium chloride, in hydrochloric acid solutions selectively assiststhe crystallisation of cucurbit[5]uril and cucurbit[8]uril leavingcucurbit[6]uril and cucurbit[7]uril in solution.

Any of the salt complexed cucurbitin[n]urils can be separated from theirsalt by a process of desalting on ion exchange resins such as Dowex 50.Dissolved in formic acid water, the mixtures are loaded onto the resinand the salts eluted with dilute hydrochloric acid/formic acid solutionsuntil satisfactory salt removal and then the final recover, of thecucurbit[n]uril is achieved by elution with 5M or higher of aqueoushydrochloric acid.

Chromatographic Separation

Both Thin Layer Chromatography (TLC) and High Pressure LiquidChromatography (HPLC) have demonstrated ability to separate out variousoligomers of cucurbit[n]uril. Both of these systems are under continuinginvestigation. TLC using a silica stationary phase and 0.1M Hydrochloricacid as the mobile phase resulted in a mixture of cucurbit[n]urilsseparating into several bands. HPLC separation has been attempted usinga C-18 stationary phase and 0.5M Na₂SO₄ mobile phase. The retentiontimes of recrystallised samples of cucurbit[6]uril and cucurbit[7]urilwere comparable with peaks found in mixed samples of crudecucurbit[n]urils.

In a further aspect, the present invention provides a method forseparating a mixture of cucurbit[n]urils, where n=4 to 10, by dissolvingthe mixture of cucurbit[n]urils and subjecting the thus-formed solutionof cucurbit[n]urils to chromatographic separation. This method may alsobe used to separate mixtures of cucurbit[s,u]urils.

In addition, polymer resins as chromatographic supports, such as. Dowexor Sephadex ion exchange columns or polyamines are effective in thepurification of cucurbit[n]urils. The eluant most commonly used was30-50% aqueous formic acid or a mixture of formic acid 98% and aqueoushydrochloric acid 0.5M in a ratio of 1:2 respectively. Samples sizes of1 to 2 gm were able to be purified on a bed of 25 cm of resin.

In order to more fully understand the present invention, the proposedreaction mechanism will be discussed hereunder. It is to be understoodthat the following reaction mechanism is a proposed mechanism and thepresent invention should not be considered to be limited thereto. Theproposed reaction mechanism hereunder should be read, in conjunctionwith FIGS. 1a, 1 b, 1 c and 1 d.

The synthesis of cucurbit[n]uril or substituted cucurbit[n]uril (where nequals the number of glycouril units marking up cucurbituril) is an acidcatalysed process. In the mechanism detailed below the first importantintermediate 1 has been isolated and is the reaction of a glycouril withfour equivalents of formaldehyde. The dehydration of this tetrol to thecyclic diether 2 has been demonstrated by the isolation of pure 2 whereR=phenyl. The intermediates A or B are both produced through a series ofacid catalysed steps. This mechanism is not prescriptive, as it ispossible for either A or B to be produced without going through 1 or 2.Similarly, it is possible for glycouril units to begin linking on oneside prior to reaction with formaldehyde on the other. This is a dynamicprocess with multiple reversible reaction steps. The mechanism shownhere is only to be considered representative of the many possibilities.

The reaction from glycoluril to cucurbit[n]uril involves a number ofintermediates produced through reversible reaction steps. The influencesacting on the balance of these reversible steps are man, and some can bemanipulated at a variety of points there by effecting the out come ofthe reaction.

EXAMPLES

The following examples illustrate preferred embodiments of the presentinvention:

Example 1

Synthesis of Cucurbit[n]urils

1.5 g—glycoluril

6.9 ml—mineral acid (hydrochloric 36%, hydrobromic 48%, hydriodic 47% orsulphuric acid 98% or 50%) or organic acid (para toluene sulphonic acid)

1.5 ml—aqueous formaldehyde 30%

5 mmol—of the corresponding alkali metal halide, ammonium halide or thecorresponding sulphates in the case of sulphuric acid or alkali metaltosylates

600 mg—red phosphorus (this was added to reaction mixtures whenhydriodic acid was used).

The glycoluril (1.5 gm, 10.6 mmol) was dissolved or suspended in theappropriate acid (6.9 ml. Then in the cases where a salt was used tomanipulate reaction products the alkali metal ion or ammonium salt (5mmol) with the corresponding anion appropriate to the acid was added. Tothis mixture at room temperature was added formaldehyde (1.5 ml) andwithin 5-10 min. the mixture set as a gel (note 1). After standing 3 hrs(note 2), heat was applied raising the temperature to 100° C. (note 3)whereby the gel liquefied. Heating and stirring was maintained for 2-3hr (note 4). The reaction mixtures were cooled and in the case of HCland HBr all volatiles were removed in vacuo at temperatures no higherthan 50° C. The residues were dissolved in the appropriate acid andevaporated again, this was repeated twice (note 5).

For remaining acids, the products were isolated by adding methanol (10ml) and collecting the resultant precipitate by filtration. The solidmaterial was washed with methanol and acetone and air dried. The redphosphorus was removed by filtration before the addition of methanol.

Products have been isolated by a process of recrystallisation usinghydrochloric acid or hydrobromic acid at varying concentrations toeffect crystallisation. The total yield was >90% except in the case ofhydriodic acid where yields were 30-80% depending on the salt used. Inall cases the range of isomers was produced ie cucurbit[n]urils withn=4, 5, 6, 7, 8, 9, etc. The maximum production of each of these wasachieved as follows:

n=4, <=1% in varying amounts under all conditions,

n=5, 55-75%, with NaI, KI, or RbI in hydriodic acid,

n=6, 80%, with CsCl in hydrochloric acid,

n=7, 52-65%, with no salts or with LiI in hydriodic acid,

n=8, 7-9%, with LiBr, or RbBr in hydrobromic acid, or LiOTs in aqueouspTsOH,

n=9, <=5%, with NH₄Cl in hydrochloric acid,

n>=10, <=2%, in varying amounts under all conditions.

Notes A

1. Following the addition of formaldehyde there is an exothermicreaction. On larger scale the reaction mixture is cooled in an ice bath.Formaldehyde can be substituted by paraformaldehyde or trioxane or anyformaldehyde producing precursor.

2. Proceeding to the next stage of the reaction procedure after 1 hr or1 month at room temperature makes little difference to the out comeexcept in the case of concentrated sulphuric acid where the reactioncontinues to cucurbit[n]urils at room temperature.

3. A reaction temperature of 60° C. and above is sufficient to givecucurbit[n]urils but at the lower temperatures with extended reactiontimes to achieve completion, up to 60hrs. The given yields above for thelarger unit cucurbit[>=7]uril are on average increased a further 50% onthe tabled yields.

4. In some cases pressure was generated during heating. In the event ofa pressure build up the pressure was released

5. The repeated dissolving and evaporation was primarily carried out toremove excess formaldehyde and volatile formaldehyde by products.

Example 2

Synthesis Cucurbit[s,u]urils

The same templating controls are applied to substituted cucurbit[n]urilseither by the above method where glycoluril used is substituted or asdescribed below:

A mixture of tetracyclic ethers (2.5 mmol) and glycoluril (0.355 gm, 2.5mmol) was dissolved or suspended in the appropriate acid (6.9 ml) (note1). Then in the cases where a salt was used to manipulate reactionproducts the alkali metal ion or ammonium salt (5 mmol) with thecorresponding anion appropriate to the acid was added. Heat was thenapplied to the reaction mixture, which was maintained at a temperatureof 100° C. for 3hrs (Note 2). The reaction mixture was cooled to roomtemperature and the products were isolated by adding methanol (10 ml)and collecting the resultant precipitate by filtration. The solidmaterial was washed with methanol and acetone and air dried. Furtherpurification was effected by recrystalisation from aqueous hydrochloricacid or hydrobromic acid or dissolving in formic acid and precipitatingby the addition of water.

The composition of these mixed substituted cucurbit[n]urils wasdetermined by Electrospray Mass Spectroscopy.

Notes B

1. The tetracyclic ether refers to a compound of the formula shown inbox 2 in FIG. 1a where the substituents R are alkyl aryl, phenanthrolineor pyridyl.

2. Para toluene sulphonic acid was the acid of choice for thetetracyclic ethers where R equals aryl or pyridyl and the temperature ofthe reaction mixture was maintained at 110° C.

3.

Example 3

Analysis of Cucurbituril Mixture

The analysis of the cucurbituril reaction mixture is routinely carriedout by ¹³C NMR. The present inventors have been able to achieve thex-ray crystal structure for cucurbit[5]uril. cucurbit[8]uril andcucurbit[10]uril. These are shown in FIG. 5a, in which Formula 12 iscucurbit[5]uril. Formula 13 is cucurbit[8]uril and Formula 14 iscucurbit[10]uril. Waters, salts etc of crystallisation are not shown.

(Cucurbit[6]uril is well established in the literature.) Solutions ofpure cucurbit[7]uril, as determined by ¹³C NMR have been prepared andElectro-Spray Mass Spectroscopy has confirmed the presence of onlycucurbit[7]uril. (While pure cucurbit[7]uril is a crystalline materialit is difficult to grow crystals of X-ray quality.) From these purecompounds the inventors have observed a trend in the ¹³C NMR chemicalshift of both the methylene and methine carbons of the cucurbit[n]uril.This trend has allowed us to identify cucurbit[9]uril, cucurbit[11]uriland cucurbit[12]uril in the reaction mixture. The table below shows theobserved ¹³C cehmical shifts for the unambiguously identifiedcucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril andcucurbit[10]uril. The predicted and observed values for cucurbit[9]uril,cucurbit[11]uril, cucurbit[12]uril and cucurbit[13]uril are alsoprovided.

Methine C Methine C Methylene C Methylene C Curcurbit[n]uril Observed*Calc'd Observed* Calc'd n = (ppm) (ppm) (ppm) (ppm) 4 — 68.54 — 48.75 569.84 69.87 50.58 50.68 6 70.98 70.96 52.29 52.17 7 71.90 71.88 53.4853.43 8 72.70 72.68 54.49 54.53 9 73.38 55.49 10 73.98 74.01 56.32 56.3511 74.58 57.13 12 75.10 57.84 13 75.58 58.50 *These values were recordedon pure isolated materials.

The results of this Table are graphically shown in FIGS. 6 and 7. Usingthis information the inventors have now identified cucurbit[9]uril(methine carbon 73.45 ppm and methylene carbon 55.42 ppm) in standardreaction mixtures. Cucurbit[11]uril and cucurbit[12]uril have only beenobserved by the methylene carbon when ¹³C labelled formaldehyde was usedas a reactant. Under these conditions the cucurbit[11]uril methylenecarbon was observed at 56.86 ppm and the cucurbit[12]uril methylenecarbon was observed at 57.75 ppm.

The inventors have routinely used the integration of ¹³C NMR over themethine region of the spectra to determine the relative amounts of eachcucurbit[n]uril in the mixture. In doing so it was assumed that thesignal response for each species is related to the number of methinecarbons for that cucurbit[n]uril and that there is little difference insignal response between the different cucurbit[n]urils. Theintegration-percent is then directly proportional to the mass percent ofeach component.

Example 4

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (250 ml and hydrochloric acid (36% w/v, 2000 mL) were placedin a reaction flask. Formalin (40% w/v) (250 μL) was added in oneportion and the reaction mixture heated to 100° C. for 15 hours. Thereaction mixture was cooled and the products were collected by theremoval of solvent on a rotary evaporator.

Yield ˜30% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 58% cucurbit[6]uril 42% cucurbit[7]uril %cucurbit[8]uril % cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 5

Synthesis of Cucurbit[n]urils in Sulfuric Acid.

Glycoluril (500 mg) and sulfuric acid (9 M, 500 mL) were placed in areaction flask. Formalin (40% w/v) (250 μL) was added in one portion andthe reaction mixture heated to 100° C. for 15 hours. The reactionmixture was cooled and the products were precipitated by addition ofmethanol and

Yield ˜85% by NMR

Approximate, Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 21% cucurbit[6]uril 64% cucurbit[7]uril 14%cucurbit[8]uril 1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 6

Synthesis of Cucurbit[n]urils in Sulfuric Acid.

Glycoluril (1.5 g) and sulfuric acid (9 M, 6.9 mL) were placed in areaction flask. Formalin (40% w/v) (1.5 mL) was added in one portion andthe reaction mixture heated to 100° C. for 3 hours. The reaction mixturewas cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 26% cucurbit[6]uril 49% cucurbit[7]uril 19%cucurbit[8]uril 6% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 7

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (77 mg) and hydrochloric acid (10 M, 0.4 mL) were placed in areaction flask. Paraformaldehyde (33 mg) was added in one portion andthe reaction mixture heated to 105° C. for 2.5 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 19% cucurbit[6]uril 54% cucurbit[7]uril 21%cucurbit[8]uril 6% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 8

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (77 mg) and hydrochloric acid (9 M, 0.4 mL) were placed in areaction flask. Paraformaldehyde (33 m) was added in one portion and thereaction mixture heated to 105° C. for 2.5 hours. The reaction mixturewas cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 18% cucurbit[6]uril 56% cucurbit[7]uril 19%cucurbit[8]uril 6% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 9

Synthesis or Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (77 mg) and hydrochloric acid (8 M, 0.4 mL) were placed in areaction flask. Paraformaldehyde (33 mg) was added in one portion andthe reaction mixture heated to 105° C. for 2.5 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 15% cucurbit[6]uril 58% cucurbit[7]uril 23%cucurbit[8]uril 4% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 10

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (77 m) and hydrochloric acid (7 M, 0.4 mL) were placed in areaction flask. Paraformaldehyde (33 mg) was added in one portion andthe reaction mixture heated to 105° C. for 2.5 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 18% cucurbit[6]uril 57% cucurbit[7]uril 23%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 11

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (77 mg) and hydrochloric acid (5 M, 0.4 mL) were placed in areaction flask. Paraformaldehyde (33 mg) was added in one portion andthe reaction mixture heated to 105° C. for 2.5 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 10% cucurbit[6]uril 60% cucurbit[7]uril 27%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 12

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (2.4 g) and hydrochloric acid (36% w/v, 2 mL) were placed ina reaction flask. Formalin (40% w/v) (2.4 mL) was added in one portionand the reaction mixture heated to 110° C. for 3 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by 1¹³C NMR (% of recovered product)

cucurbit[5]uril 6% cucurbit[6]uril 60% cucurbit[7]uril 30%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 13

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (2.4 g) and hydrochloric acid (36 w/v, 2 mL) were placed in areaction flask. Formalin (40% w/v) (2.4 mL) was added in one portion andthe reaction mixture heated to 110° C. for 18 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 6% cucurbit[6]uril 60% cucurbit[7]uril 30%cucurbit[8]uril 2% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 14

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (2.1 g) and hydrochloric acid (36% w/v, 3 mL) were placed ina reaction flask. Paraformaldehyde (887 mg) was added in one portion andthe reaction mixture heated to 110° C. for 18 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 9% cucurbit[6]uril 52% cucurbit[7]uril 29%cucurbit[8]uril 8% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 15

Synthesis of Cucurbit[n]urils in Hydrobromic Acid.

Glycoluril (2.1 g) and hydrobromic acid (48% w/v, 3 mL) were placed in areaction flask. Paraformaldehyde (887 mg) was added in one portion andthe reaction mixture heated to 100° C. for 18 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 8% cucurbit[6]uril 50% cucurbit[7]uril 29%cucurbit[8]uril 12% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 16

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (105 mg) and hydrochloric acid (36% w/v, 0.4 mL) were placedin a reaction flask. Formalin (40% w/v) (105 μL) was added in oneportion and the reaction mixture heated to 60° C. for 65 hours. Thereaction mixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 4% cucurbit[6]uril 64% cucurbit[7]uril 23%cucurbit[8]uril 9% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 17

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (77 m) and hydrochloric acid (8 M, 0.4 mL) were placed in areaction flask. Paraformaldehyde (33 mg) was added in one portion andthe reaction mixture heated to 105° C. for 2.5 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 13% cucurbit[6]uril 60% cucurbit[7]uril 23%cucurbit[8]uril 10% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 18

Synthesis of Cucurbit[n]urils in Phosphoric Acid.

Glycoluril (1.5 g) and phosphoric acid (conc, 6.9 mL) were placed in areaction flask. Formalin (40% w/v) (1.5 mL) was added in one portion andthe reaction mixture heated to 100° C. for 18 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered products

cucurbit[5]uril 10% cucurbit[6]uril 60% cucurbit[7]uril 28%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 19

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (1.02 g) and hydrochloric acid (36 w/v, 0.6 mL) were placedin a reaction flask. Paraformaldehyde (430 mg) was added in one portionand the reaction mixture heated to 100° C. for 15 hours. The reactionmixture was cooled and the products were analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 4% cucurbit[6]uril 53% cucurbit[7]uril 27%cucurbit[8]uril 10% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 20

Synthesis of Cucurbit[n]urils in Deuterated Sulfuric Acid.

Glycoluril (78 mg) and deuterated sulfuric acid (conc, 0.4 mL) wereplaced in a reaction flask. Formalin (40% w/v) (73 μL) was added in oneportion and the reaction mixture heated to n° C. for 2 months. Thereaction mixture was cooled and the products were analysed by ¹³C NMR.

Yield >9% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril >95% cucurbit[7]uril <1%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 21

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (108 mg) and hydrochloric acid (36% w/v, 0.4 mL) were placedin a reaction flask. Formalin (40% w/v) (108 μL) was added in oneportion kept at room temperature for month. The products were analysedby ¹³C NMR.

Yield No cucurbiturils present NMR suggests oligomeric product.

Example 22

Synthesis of Cucurbit[n]urils in Hydrochloric Acid.

Glycoluril (1000 g) and hydrochloric acid (36% w/v, 1420 mL) were placedin a reaction flask. Paraformaldehyde (422 g) was added in one portionand the reaction mixture heated to 105° C. for 18 hours. The reactionmixture was cooled and the products were collected by the removal ofsolvent on a rotary evaporator.

Yield quantitative mass recovery and >98% cucurbit[n]urils by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 19% cucurbit[6]uril 47% cucurbit[7]uril 27%cucurbit[8]uril 6% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 23

Synthesis of Cucurbit[n]urils in p-toluenesulfonic Acid.

Glycoluril (1 g) and p-toluenesulfonic acid (˜90% w/w, 6.9 g) wereplaced in a reaction flask. Formalin (40% w/v) (1 mL mg) was added inone portion and the reaction mixture heated to 100° C. for 3 hours. Thereaction mixture was cooled and the products were precipitated byaddition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 6% cucurbit[6]uril 68% cucurbit[7]uril 20%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 24

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid.

Glycoluril (146.5 mg) and methane sulfonic acid (neat, 1.5 mL) wereplaced in a reaction flask. Paraformaldehyde (65.5 mg) was added in oneportion and the reaction mixture heated to 90° C. for 22 hours. Thereaction mixture was cooled and the collected using a centrifuge. Thecollected solid was then dried at 80° C. overnight.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 6% cucurbit[6]uril 52% cucurbit[7]uril 33%cucurbit[8]uril 9% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 25

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid.

Glycoluril (197.6 mg) and methane sulfonic acid (neat, 1.5 mL) wereplaced in a reaction flask. Paraformaldehyde (91.1 mg) was added in oneportion and the reaction mixture heated to 90° C. for 23.5 hours. Thereaction mixture was cooled and the collected using a centrifuge. Thecollected solid was then dried at 80° C. overnight.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 8% cucurbit[6]uril 54% cucurbit[7]uril 30%cucurbit[8]uril 8% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 26

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid.

Glycoluril (302.6 mg) and methane sulfonic acid (neat, 1.5 mL) wereplaced in a reaction flask. Paraformaldehyde (130.3 mg) was added in oneportion and the reaction mixture heated to 90° C. for 23.5 hours. Thereaction mixture was cooled and the collected using a centrifuge. Thecollected solid was then dried at 80° C. overnight.

Yield >99% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 3% cucurbit[6]uril 54% cucurbit[7]uril 32%cucurbit[8]uril 11% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 27

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid.

Glycoluril (497.3 mg) and methane sulfonic acid (neat, 1.5 mL) wereplaced in a reaction flask. Paraformaldehyde (204.0 mg) was added in oneportion and the reaction mixture heated to 90° C. for 25 hours. Thereaction mixture was cooled and the collected using a centrifuge. Thecollected solid was then dried at 80° C. overnight.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 0% cucurbit[6]uril 77% cucurbit[7]uril 23%cucurbit[8]uril 0% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 28

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid.

Glycoluril (144.6 mg) and methane sulfonic acid (neat, 1.5 mL) wereplaced in a reaction flask. Paraformaldehyde (61.3 mg) was added in oneportion and the reaction mixture heated to 70° C. for 22.5 hours. Thereaction mixture was cooled and the collected using a centrifuge. Thecollected solid was then dried at 80° C. overnight.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 0% cucurbit[6]uril 49% cucurbit[7]uril 34%cucurbit[8]uril 17% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 29

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid.

Glycoluril (145.2 mg) and methane sulfonic acid (neat, 1.5 mL) wereplaced in a reaction flask. Paraformaldehyde 162.9 mg) was added in oneportion and the reaction mixture heated to 80° C. for 24 hours. Thereaction mixture was cooled and the collected using a centrifuge. Thecollected solid was then dried at 80° C. overnight.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 4% cucurbit[6]uril 56% cucurbit[7]uril 28%cucurbit[8]uril 11% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 30

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid.

Glycoluril (142.5 mg) and methane sulfonic acid (neat, 1.5 mL) wereplaced in a reaction flask. Paraformaldehyde (60.7 m) was added in oneportion and the reaction mixture heated to 100° C. for 25 hours. Thereaction mixture was cooled and the collected using a centrifuge. Thecollected solid was then dried at 80° C. overnight.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 3% cucurbit[6]uril 59% cucurbit[7]uril 32%cucurbit[8]uril 6% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 31

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid.

Glycoluril (148.3 mg) and methane sulfonic acid (neat, 1.5 mL) wereplaced in a reaction flask. Paraformaldehyde (60.2 m,) was added in oneportion and the reaction mixture heated to 110° C. for 27 hours. Thereaction mixture was cooled and the collected using a centrifuge. Thecollected solid was then dried at 80° C. overnight.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (% of recovered product)

cucurbit[5]uril 0% cucurbit[6]uril 93% cucurbit[7]uril 7%cucurbit[8]uril 0% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 32

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid Using o-carboraneas an Added Template.

Glycoluril (146.9 mg), methane sulfonic acid (neat, 1.5 mL) ando-carborane (˜18 mg) were placed in a reaction flask. Paraformaldehyde(64.2 mg) was added in one portion and the reaction mixture heated to90° C. for 22.5 hours. The reaction mixture was cooled and the productswere pecipitated by addition of ethanol and collected using acentrifuge. The collected solid was then dried at 80° C. overnight andanalysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 5% cucurbit[6]uril 52% cucurbit[7]uril 33%cucurbit[8]uril 10% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 33

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid Using o-carboraneas an Added Template.

Glycoluril (200.5 mg), methane sulfonic acid (neat, 1.5 mL) ando-carborane (102.7 mg) were placed in a reaction flask. Paraformaldehyde(94.2 mg) was added in one portion and the reaction mixture heated to90° C. for 24 hours. The reaction mixture was cooled and the productswere pecipitated by addition of ethanol and collected using acentrifuge. The collected solid was then dried at 80° C. overnight andanalysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 8% cucurbit[6]uril 53% cucurbit[7]uril 29%cucurbit[8]uril 10% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 34

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid Using o-carboraneas an Added Template.

Glycoluril (299.0 mg), methane sulfonic acid (neat, 1.5 mL) ando-carborane (152.4 mg) were placed in a reaction flask. Paraformaldehyde(126.2 mg) was added in one portion and the reaction mixture heated to90° C. for 24 hours. The reaction mixture was cooled and the productswere pecipitated by addition of ethanol and collected using acentrifuge. The collected solid was then dried at 80° C. overnight andanalysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 3% cucurbit[6]uril 57% cucurbit[7]uril 33%cucurbit[8]uril 7% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 35

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid Using o-carboraneas an Added Template.

Glycoluril (501.9 mg), methane sulfonic acid (neat, 15 mL) ando-carborane (166.2 mg) were placed in a reaction flask. Paraformaldehyde(207.9 mg) was added in one portion and the reaction mixture heated to90° C. for 25 hours. The reaction mixture was cooled and the productswere pecipitated by addition of ethanol and collected using acentrifuge. The collected solid was then dried at 80° C. overnight andanalysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 0% cucurbit[6]uril 63% cucurbit[7]uril 28%cucurbit[8]uril 9% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 36

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid Using o-carboraneas an Added Template.

Glycoluril (145.0 mg), methane sulfonic acid (neat, 1.5 mL) ando-carborane (53.4 mg) were placed in a reaction flask. Paraformaldehyde(62.5 mg) was added in one portion and the reaction mixture heated to70° C. for 2.5 hours. The reaction mixture was cooled and the productswere pecipitated by addition of ethanol and collected using acentrifuge. The collected solid was then dried at 80° C. overnight andanalysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 0% cucurbit[6]uril 48% cucurbit[7]uril 32%cucurbit[8]uril 20% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 37

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid Using o-carboraneas an Added Template.

Glycoluril (146.9 mg), methane sulfonic acid (neat, 1.5 mL) ando-carborane (53.4 mg) were placed in a reaction flask. Paraformaldehyde(64.0 mg) was added in one portion and the reaction mixture healed to80° C. for 24 hours. The reaction mixture was cooled and the productswere pecipitated by addition of ethanol and collected using acentrifuge. The collected solid was then dried at 80° C. overnight andanalysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 4% cucurbit[6]uril 48% cucurbit[7]uril 29%cucurbit[8]uril 19% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 38

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid Using o-carboraneas an Added Template.

Glycoluril (142.7 mg), methane sulfonic acid (neat, 1.5 mL) ando-carborane (48.6 mg) were placed in a reaction flask. Paraformaldehyde(60.7 mg) was added in one portion and the reaction mixture heated to100° C. for 25 hours. The reaction mixture was cooled and the productswere pecipitated by addition of ethanol and collected using acentrifuge. The collected solid was then dried at 80° C. overnight andanalysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 2% cucurbit[6]uril 53% cucurbit[7]uril 31%cucurbit[8]uril 14% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 39

Synthesis of Cucurbit[n]urils in Methane Sulfonic Acid Using o-carboraneas an Added Template.

Glycoluril (145.5 mg), methane sulfonic acid (neat, 1.5 mL) ando-carborane (49.9 mg) were placed in a reaction flask. Paraformaldehyde(60.7 mg) was added in one portion and the reaction mixture heated to110° C. for 27 hours. The reaction mixture was cooled and the productswere pecipitated by addition of ethanol and collected using acentrifuge. The collected solid was then dried at 80° C. overnight andanalysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 0% cucurbit[6]uril 65% cucurbit[7]uril 26%cucurbit[8]uril 9% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 40

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using Thioacetamideas an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v 0.7 mL) andthioacetamide (12.8 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 0% cucurbit[6]uril 64% cucurbit[7]uril 36%cucurbit[8]uril 0% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 41

Synthesis of Cucurbit[n]urils in Hydrochloric Acid UsingN-(1-napthyl)ethylenediamine as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) andN-(1-napthyl)ethylenediamine (44.1 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 12% cucurbit[6]uril 53% cucurbit[7]uril 23%cucurbit[8]uril 12% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 42

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using 2,2′-biquinoylas an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) and2,2′-biquinoyl (43.6 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 6% cucurbit[6]uril 62% cucurbit[7]uril 26%cucurbit[8]uril 6% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 43

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using p-bromoanilineas an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) andp-bromoaniline (29.3 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 11% cucurbit[6]uril 36% cucurbit[7]uril 36%cucurbit[8]uril 15% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 44

Synthesis of Cucurbit[n]urils in Hydrochloric Acid UsingTetrabutylammonium Chloride as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) andtetrabutylammonium chloride (47.3 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 5% cucurbit[6]uril 55% cucurbit[7]uril 25%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 45

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using Taurine as anAdded Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) and taurine(1.3 mg) were placed in a reaction flask. Paraformaldehyde (60.0 mg) wasadded in one portion and the reaction mixture heated to 95° C. for 4hours. The reaction mixture was cooled and the products were collectedby the removal of solvent on a rotary evaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 16% cucurbit[6]uril 51% cucurbit[7]uril 23%cucurbit[8]uril 10% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 46

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using BlueTetrazolium as an Added Template.

Glycoluril (142.1 mg, hydrochloric acid (36% w/v, 0.7 mL) and bluetetrazolium (123.7 mg) were placed in a reaction flask. Paraformaldehyde(60.0 mg) was added in one portion and the reaction mixture heated to95° C. for 4 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 7% cucurbit[6]uril 55% cucurbit[7]uril 23%cucurbit[8]uril 10% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 47

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using2-amino-3-methyl benzoic acid as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) and2-amino-3-methyl benzoic acid (25.7 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 5% cucurbit[6]uril 55% cucurbit[7]uril 25%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 48

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Usingindol-3-aldehyde as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) andindol-3-aldehyde (24.7 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 3% cucurbit[6]uril 70% cucurbit[7]uril 25%cucurbit[8]uril 2% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 49

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using Cystine as anAdded Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) and cystine(40.9 mg) were placed in a reaction flask. Paraformaldehyde (60.0 mg)was added in one portion and the reaction mixture heated to 95° C. for 4hours. The reaction mixture was cooled and the products were collectedby the removal of solvent on a rotary evaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 5% cucurbit[6]uril 55% cucurbit[7]uril 25%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 50

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Usingp-acetamidoaniline as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) andp-acetamidoaniline (25.5 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 5% cucurbit[6]uril 55% cucurbit[7]uril 25%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 51

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using p-amninophenolas an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) andp-aminophenol (18.6 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 13% cucurbit[6]uril 39% cucurbit[7]uril 36%cucurbit[8]uril 12% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 52

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using Acetamide as anAdded Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) and acetamide(10.0 mg) were placed in a reaction flask. Paraformaldehyde (60.0 mg)was added in one portion and the reaction mixture heated to 95° C. for 4hours. The reaction mixture was cooled and the products were collectedby the removal of solvent on a rotary evaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 9% cucurbit[6]uril 31% cucurbit[7]uril 39%cucurbit[8]uril 17% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 53

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using4-aminoacetophenone as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) and4-aminoacetophenone (23.0 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  9% cucurbit[6]uril 44.5%   cucurbit[7]uril 35%cucurbit[8]uril 12% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 54

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using4-dimethylaminobenzaldehyde as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) and4-dimethylaminobenzaldehyde (25.4 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 4 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 5% cucurbit[6]uril 55% cucurbit[7]uril 25%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 55

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using2-aminobenzimadazol as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) and2-aminobenzimadazol (22.6 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 2 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 9% cucurbit[6]uril 40% cucurbit[7]uril 30%cucurbit[8]uril 11% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 56

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Usingbis-(4,4′-bipyridyl)-α,α′-p-xylene as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) andbis-(4,4′-bipyrndyl)-α,α′-p-xylene (110.8 mg) were placed in a reactionflask. Paraformaldehyde (60.0 mg) was added in one portion and thereaction mixture heated to 95° C. for 2 hours. The reaction mixture wascooled and the products were collected by the removal of solvent on arotary evaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 8% cucurbit[6]uril 42% cucurbit[7]uril 46%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 57

Synthesis of Cucurbit[n]urils in Hydrochloric Acid UsingTetraethylammonium Chloride as an Added Template.

Glycoluril (142.1 mg), hydrochloric acid (36% w/v, 0.7 mL) andtetraethylammonium chloride (28.2 mg) were placed in a reaction flask.Paraformaldehyde (60.0 mg) was added in one portion and the reactionmixture heated to 95° C. for 2 hours. The reaction mixture was cooledand the products were collected by the removal of solvent on a rotaryevaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 0% cucurbit[6]uril 10% cucurbit[7]uril 70%cucurbit[8]uril 18% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 58

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using AmmoniumChloride as an Added Template.

Glycoluril (1.49 g), hydrochloric acid (36% w/v, 6.9 mL) and ammoniumchloride (280 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 15% cucurbit[6]uril 62% cucurbit[7]uril 20%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 59

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using LithiumChloride as an Added Template.

Glycoluril (1.49 g), hydrochloric acid (36% w/v, 6.9 mL) and lithiumchloride (211 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 7% cucurbit[6]uril 68% cucurbit[7]uril 22%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 60

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using Sodium Chlorideas an Added Template.

Glycoluril (1.49 g), hydrochloric acid (36% w/v, 6.9 mL) and sodiumchloride (292 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 3% cucurbit[6]uril 73% cucurbit[7]uril 21%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 61

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using PotassiumChloride as an Added Template.

Glycoluril (1.49 g), hydrochloric acid (36% w/v, 6.9 mL) and potassiumchloride (372 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 24% cucurbit[6]uril 61% cucurbit[7]uril 14%cucurbit[8]uril 2% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 62

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using RubidiumChloride as an Added Template.

Glycoluril (1.49 g), hydrochloric acid (36% w/v, 6.9 mL) and rubidiumchloride (604 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 14% cucurbit[6]uril 70% cucurbit[7]uril 15%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 63

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using CaesiumChloride as an Added Template.

Glycoluril (1.49 g) hydrochloric acid (36% w/v, 6.9 mL) and caesiumchloride (842 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 4% cucurbit[6]uril 79% cucurbit[7]uril 16%cucurbit[8]uril 1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 64

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using Ammonium Bromideas an Added Template.

Glycoluril (1.49 g), hydrobromic acid (48% w/v, 6.9 mL) and ammoniumbromide (490 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 8% cucurbit[6]uril 66% cucurbit[7]uril 23%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 65

Synthesis of Cucurbit[n]urils in Hydrobromic Acid.

Glycoluril (1.49 g) and hydrobromic acid (48% w/v, 6.9 mL) were placedin a reaction flask. Formalin (40% w/v) (1.5 mL) was added in oneportion and the reaction mixture heated to 100° C. for 3 hours. Thereaction mixture was cooled and the products were collected by theremoval of solvent on a rotary evaporator and analysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 5% cucurbit[6]uril 59% cucurbit[7]uril 30%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 66

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using Lithium Bromideas an Added Template.

Glycoluril (1.49 g) hydrobromic acid (48% w/v, 6.9 mL) and lithiumbromide (435 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 7% cucurbit[6]uril 49% cucurbit[7]uril 36%cucurbit[8]uril 7% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 67

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using Sodium Bromideas an Added Template.

Glycoluril (1.49 g), hydrobromic acid (48% w/v, 6.9 mL) and sodiumbromide (515 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 16% cucurbit[6]uril 44% cucurbit[7]uril 35%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 68

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using Sodium Bromide,as an Added Template.

Glycoluril (1.49 g), hydrobromic acid (48% w/v, 6.9 mL) and sodiumbromide (5000 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 40% cucurbit[6]uril 51% cucurbit[7]uril 9%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 69

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using PotassiumBromide as an Added Template.

Glycoluril (1.49 g) hydrobromic acid (48% w/v, 6.9 mL) and potassiumbromide (595 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 36% cucurbit[6]uril 44% cucurbit[7]uril 18%cucurbit[8]uril 2% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 70

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using Rubidium Bromideas an Added Template.

Glycoluril (1.49 g), hydrobromic acid (48% w/v, 6.9 mL) and rubidiumbromide (827 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 25% cucurbit[6]uril 43% cucurbit[7]uril 24%cucurbit[8]uril 8% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 71

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using Caesium Bromideas an Added Template.

Glycoluril (1.49 g), hydrobromic acid (48% w/v, 6.9 mL) and caesiumbromide (1070 mg were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 3 hours. The reaction mixture was cooled and the productswere collected by the removal of solvent on a rotary evaporator andanalysed by NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 15% cucurbit[6]uril 59% cucurbit[7]uril 23%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 72

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using AmmoniumChloride as an Added Template.

Glycoluril (1.49 g), hydrochloric acid (36% w/v, 6.9 mL) and ammoniumchloride (280 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to 60°C. for 60 hours. The reaction mixture was cooled and the products werecollected by the removal of solvent on a rotary evaporator and analysedby NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 11% cucurbit[6]uril 60% cucurbit[7]uril 21%cucurbit[8]uril 8% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 73

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using Rubidium Bromideas an Added Template.

Glycoluril (1.49 g), hydrobromic acid (48% w/v, 6.9 mL) and rubidiumbromide (827 mg). were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to 60°C. for 84 hours. The reaction mixture was cooled and the products werecollected by the removal of solvent on a rotary evaporator and analysedby NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 34% cucurbit[6]uril 39% cucurbit[7]uril 19%cucurbit[8]uril 9% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 74

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using PotassiumChloride as an Added Template.

Glycoluril (250 g), hydrochloric acid (36% w/v, 6.9 mL) and potassiumchloride (62 g) were placed in a reaction flask. Paraformaldehyde (110g) was added in one portion and the reaction mixture heated to 95° C.for 4 hours. The reaction mixture was cooled and the products werecollected by the removal of solvent on a rotary evaporator and analysedby NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 39% cucurbit[6]uril 36% cucurbit[7]uril 20%cucurbit[8]uril 5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 75

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using PotassiumChloride as an Added Template.

Glycoluril (8 g), hydrochloric acid (36% w/v, 6.9 mL) and potassiumchloride (2.1 g) were placed in a reaction flask. Paraformaldehyde (3.5g) was added in one portion and the reaction mixture heated to 100° C.for 3.5 hours. The reaction mixture was cooled and the products werecollected by the removal of solvent on a rotary evaporator and analysedby NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 26% cucurbit[6]uril 56% cucurbit[7]uril 15%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 76

Synthesis of Cucurbit[n]urils in Hydrobromic Acid Using Lithium Bromideas an Added Template.

Glycoluril (1.49 g), hydrobromic acid (48% w/v, 6.9 mL) and lithiumbromide (4.3 g) were placed in a reaction flask. Formalin (40% w/v) (1.5mL) was added in one portion and the reaction mixture heated to 100° C.for 3 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 13% cucurbit[6]uril 63% cucurbit[7]uril 22%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 77

Synthesis of Cucurbit[n]urils in Hydroiodic Acid.

Glycoluril (1.49 g) and hydroiodic acid (57% w/v, 6.9 mL) were placed ina reaction flask. Formalin (40% w/v) (1.5 mL) was added in one portionand the reaction mixture heated to 100° C. for 2 hours. The reactionmixture was cooled and the products were precipitated by addition ofmethanol and collected by vacuum filtration.

Yield 2.2 g

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 3% cucurbit[6]uril 72% cucurbit[7]uril 22%cucurbit[8]uril 3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 78

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Lithium Iodide asan Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and lithiumiodide (665 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5mL) was added in one portion and the reaction mixture heated to 100° C.for 2 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield 0.9 g

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 16% cucurbit[6]uril 28% cucurbit[7]uril 56%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 79

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Sodium Iodide asan Added Template.

Glycoluril (1.49 g) hydroiodic acid (57% w/v, 6.9 mL) and sodium iodide(745 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5 mL)was added in one portion and the reaction mixture heated to 100° C. for2 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 19% cucurbit[6]uril 55% cucurbit[7]uril 17%cucurbit[8]uril  9% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 80

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Potassium Iodideas an Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and potassiumiodide (825 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5mL) was added in one portion and the reaction mixture heated to 100° C.for 2 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 67% cucurbit[6]uril 22% cucurbit[7]uril 10%cucurbit[8]uril  1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 81

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Rubidium Iodideas an Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and rubidiumiodide (1060 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 2 hours. The reaction mixture was cooled and the productswere precipitated by addition of methanol and collected by vacuumfiltration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 34% cucurbit[6]uril 18% cucurbit[7]uril 48%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 82

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Caesium Iodide asan Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and caesiumiodide (1300 mg) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 1 hours. The reaction mixture was cooled and the productswere precipitated by addition of methanol and collected by vacuumfiltration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  8% cucurbit[6]uril 36% cucurbit[7]uril 53%cucurbit[8]uril  3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 83

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Red Phosphorousas an Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and redphosphorous (1 g) were placed in a reaction flask. Formalin (40% w/v)(1.5 mL) was added in one portion and the reaction mixture heated to100° C. for 2 hours. The reaction mixture was cooled and the productswere precipitated by addition of methanol and collected by vacuumfiltration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  3% cucurbit[6]uril 70% cucurbit[7]uril 23%cucurbit[8]uril  4% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 84

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Lithium Iodideand Red Phosphorous as an Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and lithiumiodide and red phosphorous (665 mg and 650 mg respectively) were placedin a reaction flask. Formalin (40% w/v) (1.5 mL) was added in oneportion and the reaction mixture heated to 100° C. for 2 hours. Thereaction mixture was cooled and the products were precipitated byaddition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 23% cucurbit[6]uril  6% cucurbit[7]uril 65%cucurbit[8]uril  6% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 85

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Sodium Iodide andRed Phosphorous as an Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and sodium iodideand red phosphorous (745 mg and 650 mg respectively) were placed in areaction flask. Formalin (40% w/v) (1.5 mL) was added in one portion andthe reaction mixture heated to 100° C. for 2 hours. The reaction mixturewas cooled and the products were precipitated by addition of methanoland collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 57% cucurbit[6]uril  9% cucurbit[7]uril 29%cucurbit[8]uril  5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 86

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Potassium Iodideand Red Phosphorous as an Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and potassiumiodide and red phosphorous (825 mg and 650 mg respectively) were placedin a reaction flask. Formalin (40% w/v) (1.5 mL) was added in oneportion and the reaction mixture heated to 100° C. for 2 hours. Thereaction mixture was cooled and the products were precipitated byaddition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 75% cucurbit[6]uril 11% cucurbit[7]uril 10%cucurbit[8]uril  3% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 87

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Rubidium Iodideand Red Phosphorous as an Added Template.

Glycoluril (1.49 g) hydroiodic acid (57% w/v, 6.9 mL) and rubidiumiodide and red phosphorous (1060 mg and 650 mg respectively) were placedin a reaction flask. Formalin (40% w/v) (1.5 mL) was added in oneportion and the reaction mixture heated to 100° C. for 2 hours. Thereaction mixture was cooled and the products were precipitated byaddition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 58% cucurbit[6]uril 20% cucurbit[7]uril 20%cucurbit[8]uril  2% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 88

Synthesis of Cucurbit[n]urils in Hydroiodic Acid Using Caesium Iodideand Red Phosphorous as an Added Template.

Glycoluril (1.49 g), hydroiodic acid (57% w/v, 6.9 mL) and caesiumiodide and red phosphorous (1300 mg and 650 mg respectively) were placedin a reaction flask. Formalin (40% w/v) (1.5 mL) was added in oneportion and the reaction mixture heated to 100° C. for 2 hours. Thereaction mixture was cooled and the products were precipitated byaddition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 21% cucurbit[6]uril 28% cucurbit[7]uril 46%cucurbit[8]uril  5% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 89

Synthesis of Cucurbit[n]urils in Sulfuric Acid Using Potassium Sulfateas an Added Template.

Glycoluril (1.49 g), sulfuric acid (9 M, 6.9 mL) and potassium sulfate(436 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5 mL)was added in one portion and the reaction mixture heated to 100° C. for3 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 15% cucurbit[6]uril 66% cucurbit[7]uril 18%cucurbit[8]uril  1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 90

Synthesis of Cucurbit[n]urils in Sulfuric Acid Using Potassium Sulfateas an Added Template.

Glycoluril (1.49 g), sulfuric acid (9 M, 6.9 mL) and potassium sulfate(871 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5 mL)was added in one portion and the reaction mixture heated to 100° C. for3 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 11% cucurbit[6]uril 75% cucurbit[7]uril 15%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 91

Synthesis of Cucurbit[n]urils in Sulfuric Acid Using Potassium Sulfateas an Added Template.

Glycoluril (1.49 g) sulfuric acid (9 M, 6.9 mL) and potassium sulfate1307 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5 mL)was added in one portion and the reaction mixture heated to 100° C. for3 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 33% cucurbit[6]uril 49% cucurbit[7]uril 17%cucurbit[8]uril  2% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 92

Synthesis of Cucurbit[n]urils in Sulfuric Acid Using Potassium Sulfateas an Added Template.

Glycoluril (1.49 g), sulfuric acid (9 M, 6.9 mL) and potassium sulfate(4350 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5 mL)was added in one portion and the reaction mixture heated to 100° C. for3 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 23% cucurbit[6]uril 64% cucurbit[7]uril 13%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 93

Synthesis of Cucurbit[n]urils in Sulfuric Acid Using Lithium Sulfate asan Added Template.

Glycoluril (1.49 g), sulfuric acid (9 M, 6.9 mL) and lithium sulfate(275 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5 mL)was added in one portion and the reaction mixture heated to 100° C. for3 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  4% cucurbit[6]uril 71% cucurbit[7]uril 13%cucurbit[8]uril 24% cucurbit[9]uril  1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 94

Synthesis of Cucurbit[n]urils in Sulfuric Acid Using Lithium Sulfate asan Added Template.

Glycoluril (1.49 g), sulfuric acid (9 M, 6.9 mL) and lithium sulfate(2750 mg) were placed in a reaction flask. Formalin (40% w/v) (1.5 mL)was added in one portion and the reaction mixture heated to 100° C. for3 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 25% cucurbit[6]uril 51% cucurbit[7]uril 23%cucurbit[8]uril  1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 95

Synthesis of Cucurbit[n]urils in Hydrochloric Acid Using LithiumChloride as an Added Template.

Glycoluril (5 8), hydrochloric acid (36% w/v, 6.9 mL) and lithiumchloride (746 mg) were placed in a reaction flask. Paraformaldehyde (2.2g) was added in one portion and the reaction mixture heated to 100° C.for 4 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and collected by vacuum filtration.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 22% cucurbit[6]uril 37% cucurbit[7]uril 29%cucurbit[8]uril 12% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 96

Synthesis of Cucurbit[n]urils in p-toluenesulfonic Acid Using Lithiump-toluenesulfonate as an Added Template.

Glycoluril (400 mg), p-toluenesulfonic acid (˜95% 3.5 g) and lithiump-toluenesulfonate (157 mg) were placed in a reaction flask. Formalin(40% w/v) (0.5 mL) was added in one portion and the reaction mixtureheated to 100° C. for 3 hours. The reaction mixture was cooled and theproducts were precipitated by addition of methanol and collected byvacuum filtration.

Yield 240 mg

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 18% cucurbit[6]uril 45% cucurbit[7]uril 26%cucurbit[8]uril  9% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 97

Synthesis of Cucurbit[n]urils with Hydrochloric Acid UsingTrifluoroacetic Acid as a Solvent.

Glycoluril (144 mg), hydrochloric acid (36% w/v, 1 drop) andtrifluoroacetic acid (1 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 3 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 46% cucurbit[6]uril 54% cucurbit[7]uril <1%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 98

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using TrifluoroaceticAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 2 drops) andtrifluoroacetic acid (1 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 4 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  <1% cucurbit[6]uril 100% cucurbit[7]uril  <1%cucurbit[8]uril  <1% cucurbit[9]uril  <1% cucurbit[10]uril  <1%cucurbit[11]uril  <1%

Example 99

Synthesis of Cucurbit[n]urils with Hydrochloric Acid UsingTrifluoroacetic Acid as a Solvent.

Glycoluril (144 mg), hydrochloric acid (36% w/v, 5 drops) andtrifluoroacetic acid (1 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 5 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  <1% cucurbit[6]uril 100% cucurbit[7]uril  <1%cucurbit[8]uril  <1% cucurbit[9]uril  <1% cucurbit[10]uril  <1%cucurbit[11]uril  <1%

Example 100

Synthesis of Cucurbit[n]urils with Hydrochloric Acid UsingTrifluoroacetic Acid as a Solvent.

Glycoluril (144 mg) and trifluoroacetic acid (1 mL) were placed in areaction flask. Dry hydrochloric acid gas was then bubbled into thesolution for 15 minutes. Paraformaldehyde (63 mg) was added in oneportion and the reaction mixture heated to 90° C. for 20.5 hours. Thereaction mixture was cooled and the products were precipitated byaddition of methanol and the collected solid was then dried at 80° C.overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  <1% cucurbit[6]uril 100% cucurbit[7]uril  <1%cucurbit[8]uril  <1% cucurbit[9]uril  <1% cucurbit[10]uril  <1%cucurbit[11]uril  <1%

Example 101

Synthesis of Cucurbit[n]urils with Hydrochloric Acid UsingTrifluoroacetic Acid as a Solvent.

Glycoluril (144 mg) trifluoroacetic acid (2 mL) were placed in areaction flask. Dry hydrochloric acid gas was then bubbled into thesolution for 15 minutes. Paraformaldehyde (63 mg) was added in oneportion and the reaction mixture heated to 90° C. for 25 hours Thereaction mixture was cooled and the products were precipitated byaddition of methanol and the collected solid was then dried at 80° C.overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  <1% cucurbit[6]uril 100% cucurbit[7]uril  <1%cucurbit[8]uril  <1% cucurbit[9]uril  <1% cucurbit[10]uril  <1%cucurbit[11]uril  <1%

Example 102

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using TrifluoroaceticAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 1 drop) and trifluoroaceticacid (1.5 mL) were placed in a reaction flask. Paraformaldehyde (63 mg)was added in one portion and the reaction mixture heated to 90° C. for 3hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and the collected solid was thendried at 80° C. overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 37% cucurbit[7]uril 39%cucurbit[8]uril 24% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 103

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using TrifluoroaceticAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 2 drops) andtrifluoroacetic acid (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 23 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and hecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  <1% cucurbit[6]uril 100% cucurbit[7]uril  <1%cucurbit[8]uril  <1% cucurbit[9]uril  <1% cucurbit[10]uril  <1%cucurbit[11]uril  <1%

Example 104

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using TrifluoroaceticAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 5 drops) andtrifluoroacetic acid (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 23 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 48% cucurbit[7]uril 32%cucurbit[8]uril 20% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 105

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using TrifluoroaceticAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 5 drops) andtrifluoroacetic acid (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 3 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 57% cucurbit[7]uril 28%cucurbit[8]uril 15% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 106

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using TrifluoroaceticAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (fuming, 3 drops) and trifluoroaceticacid (1.5 mL) were placed in a reaction flask. Paraformaldehyde (63 mg)was added in one portion and the reaction mixture heated to 90° C. for25.5 hours. The reaction mixture was cooled and the products wereprecipitated by addition of methanol and the collected solid was thendried at 80° C. overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 47% cucurbit[7]uril 34%cucurbit[8]uril 20% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 107

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using MethanesulfonicAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 1 drop) and methanesulfonicacid (1.5 mL) were placed in a reaction flask. Paraformaldehyde (63 mg)was added in one portion and the reaction mixture heated to 90° C. for26 hours. The reaction mixture was cooled and the products werepecipitated by addition of ethanol and the collected solid was thendried at 80° C. overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  5% cucurbit[6]uril 62% cucurbit[7]uril 33%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 108

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using MethanesulfonicAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 5 drops) andmethanesulfonic acid (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 26 hours. The reaction mixture was cooledand the products were pecipitated by addition of ethanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  7% cucurbit[6]uril 61% cucurbit[7]uril 32%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 109

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using TrifluoroaceticAcid as a Solvent.

Glycoluril (144 m), sulfuric acid (fuming, 3 drops) and trifluoroaceticacid (1.5 mL) were placed in a reaction flask. Paraformaldehyde (63 mg)was added in one portion and the reaction mixture heated to 90° C. for26 hours. The reaction mixture was cooled and the products werepecipitated by addition of ethanol and the collected solid was thendried at 80° C. overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 47% cucurbit[7]uril 35%cucurbit[8]uril 17% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 110

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using TrifluoroaceticAcid as a Solvent.

Glycoluril (144 mg), sulfuric acid (fuming, 3 drops) and trifluoroaceticacid (1.5 mL) were placed in a reaction flask. Paraformaldehyde (63 mg)was added in one portion and the reaction mixture heated to 90° C. for26 hours. The reaction mixture was cooled and the products werepecipitated by addition of ethanol and the collected solid was thendried at 80° C. overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 47% cucurbit[7]uril 32%cucurbit[8]uril 21% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 111

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using1,1,1-trifluoroethanol as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 1 drop) and1,1,1-trifluoroethanol (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 m) was added in one portion and the reactionmixture heated to 90° C. for 25 hours. The reaction mixture was cooledand the products were pecipitated by addition of ethanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 17% cucurbit[6]uril 72% cucurbit[7]uril 11%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 112

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using1,1,1-trifluoroethanol as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 5 drops) and1,1,1-trifluoroethanol (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 25 hours. The reaction mixture was cooledand the products were pecipitated by addition of ethanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril 89% cucurbit[6]uril 11% cucurbit[7]uril <1%cucurbit[8]uril <1% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 113

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using1,1,1-trifluoroethanol as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 1 drop) and1,1,1-trifluoroethanol (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 170 hours. The reaction mixture was cooledand the products were pecipitated by addition of ethanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  <1% cucurbit[6]uril 100% cucurbit[7]uril  <1%cucurbit[8]uril  <1% cucurbit[9]uril  <1% cucurbit[10]uril  <1%cucurbit[11]uril  <1%

Example 114

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using1,1,1-trifluoroethanol as a Solvent.

Glycoluril (144 mg), sulfuric acid (98% w/v, 5 drops) and1,1,1-trifluoroethanol (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 170 hours. The reaction mixture was cooledand the products were pecipitated by addition of ethanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  <1% cucurbit[6]uril 100% cucurbit[7]uril  <1%cucurbit[8]uril  <1% cucurbit[9]uril  <1% cucurbit[10]uril  <1%cucurbit[11]uril  <1%

Example 115

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using Trifluoro AceticAcid as a Solvent and o-carborane as a Template.

Glycoluril (144 mg), sulfuric acid (98% w/v, 1 drop), o-carborane (18mg) and trifluoro acetic acid (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 25.5 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 57% cucurbit[7]uril 32%cucurbit[8]uril 11% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 116

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using Trifluoro AceticAcid as a Solvent and o-carborane as a Template.

Glycoluril (144 mg), sulfuric acid (98% w/v, 5 drops), o-carborane (18mg) and trifluoro acetic acid (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 25.5 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >99% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 50% cucurbit[7]uril 32%cucurbit[8]uril 17% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 117

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using Trifluoro AceticAcid as a Solvent and o-carborane as a Template.

Glycoluril (144 mg), sulfuric acid (98% w/v, 1 drop), o-carborane (18 m)and trifluoro acetic acid (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 20 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³C

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 51% cucurbit[7]uril 39%cucurbit[8]uril 10% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 118

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using Trifluoro AceticAcid as a Solvent and o-carborane as a Template.

Glycoluril (144 mg), sulfuric acid (98% w/v, 5 drops), o-carborane (18mg) and trifluoro acetic acid (1.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 20 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril <1% cucurbit[6]uril 47% cucurbit[7]uril 38%cucurbit[8]uril 15% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 119

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using Trifluoro AceticAcid as a Solvent and o-carborane as a Template.

Glycoluril (710 mg), sulfuric acid (98% w/v, 7.5 mL), o-carborane (18mg) and trifluoro acetic acid (1 5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 24.5 hours. The reaction mixture was cooledand the products were precipitated by addition of methanol and thecollected solid was then dried at 80° C. overnight and analysed by ¹³CNMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  3% cucurbit[6]uril 53% cucurbit[7]uril 33%cucurbit[8]uril 11% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 120

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using MethanesulfonicAcid as a Solvent and o-carborane as a Template.

Glycoluril (144 mg), sulfuric acid (98% w/v, 1 drop), o-carborane (18mg) and methanesulfonic acid (7.5 mL) were placed in a reaction flask.Paraformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 22.5 hours. The reaction mixture was cooledand the products were pecipitated by addition of ethanol and collectedusing a centrifuge. The collected solid was then dried at 80° C.overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  7% cucurbit[6]uril 53% cucurbit[7]uril 30%cucurbit[8]uril 10% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 121

Synthesis of Cucurbit[n]urils with Sulfuric Acid Using MethanesulfonicAcid as a Solvent and o-carborane as a Template.

Glycoluril (144 mg), sulfuric acid (98% w/v, 5 drops), o-carborane (18mg) and methanesulfonic acid (1.5 mL) were placed in a reaction flaskParaformaldehyde (63 mg) was added in one portion and the reactionmixture heated to 90° C. for 22.5 hours. The reaction mixture was cooledand the products were pecipitated by addition of ethanol and collectedusing a centrifuge. The collected solid was then dried at 80° C.overnight and analysed by ¹³C NMR.

Yield >98% by NMR

Approximate Yields by ¹³C NMR (mass % of recovered product)

cucurbit[5]uril  6% cucurbit[6]uril 56% cucurbit[7]uril 30%cucurbit[8]uril  8% cucurbit[9]uril <1% cucurbit[10]uril <1%cucurbit[11]uril <1%

Example 122

Preparation of Substituted Cucurbiturils

Substituted glycolurils of the following formulae were used in thissynthesis:

Examples of Mixed Cucurbit[s,u]urils

‘tetracyclic diether’ R=R′=CH₃, dimethyl; R=R′=C₆H₅, diphenyl;

dihydrophenathroline.

(1) A mixture of the dimethyl tetracyclic diether (107 mg) and caesiumchloride (71 mg) in concentrated hydrochloric acid (0.5 ml) was heatedat 100° C. for 1 hr 40 mins, to give a >85% yield of thedecamethylcucurbit[5]uril and <1% of the other sizes.

(2) A mixture of the dimethyl tetracyclic diether (97 mg) and glycoluril(54 mg) in concentrated hydrochloric acid (0.5 ml) was shaken at roomtemperature for 1 hr then heated at 100° C. for 1 hr 40 mins., at whichtime reaction was complete. The yield was determined by ¹³C NMR tobe >95% for a mixture of the methyl substituted cucurbit[s,u]urils,where s,u equals 1,4; 2,3; 3,2; 4,1; 1,5; 2,4; 3,3; 4,2; 5,1; 1,6; 2,5;3,4; 4,3; 5,2; 6,1; and s represents the unit carrying the substitution.The composition of s to u was determined by ES-MS.

(3) A mixture of the dimethyl tetracyclic diether (119 mg) glycoluril(66 mg) and caesium chloride (78 mg) in concentrated hydrochloric acid(0.5 ml) was shaken at room temperature for 1 hr then heated at 100° C.until the reaction was complete at 1 hr 20 mins. The yield by ¹³C NMRwas near quantitative. The composition of s to u was observed to bedifferent but not accurately determined.

(4) The diphenyl tetracyclic diether (1.9 gm), gylcoluril (0.71 gm) andpara toluene sulphonic acid (10.4 gm) were combined and heated to 120°C. for 3 hr. While still hot the mixture was poured into methanol (150ml) and precipitate collected by filtration. The solid materialcollected was dissolved in a minimum volume of hot formic acid and thissolution was poured into hot water and the precipitate collected to give1.32 gm of the phenyl substituted cucurbit[s,u]urils, where s,u equals1,4; 2,3; 2,4; 3,3 and s represents the unit carrying the substitution.

(6) To a suspension of the dihydrophenathroline glycoluril (530 mg) inaqueous 40% formaldehyde was added 8M hydrochloric acid (1.8 ml) and themixture stirred at room temperature for 5 hr. Then glycoluril (253 mg)was added and the mixture heated at 100° C. for 3hr. ¹³C NMR of themixture indicated a 20-30% formation of the dihydrophenanthrolinesubstituted cucurbit[s,u]urils.

Variations of these methods could conceivably be applied to anysubstituted glycoluril where the side chain is stable to the reactionconditions.

Template Function.

The controlling factors for achieving the synthesis of a variety ofcucurbiturils of differing unit sizes are postulated to be primarilyderived from a templating effect. For example, an anion is apparentlyheld in position by a metal cation or the ammonium ion. The metalcations coordinate to the carbonyls of the forming cucurbiturilintermediates (such as F, G1 and G2) or in the case of the ammoniumcation is held through hydrogen bonding to the carbonyls of theseintermediates. The larger iodide anion and its tight pairing with thelithium cation favours cucurbit[7]uril but for the more diffuse ionpairs of sodium, potassium, or rubidium, iodide does not control thesize by templating around the anion but rather templating ispredominantly controlled by the cation although this effect diminishesas the anion decreases in size. There has been found a common trendwhere the equilibrium shifts by varying combinations of anion andcations. The proton from the acid not only serves as a catalyst but alsoacts as a cation capable of hydrogen bonding to the carbonyls of theforming cucurbit[n]uril and also controlling the placement of anions.The degree of the competing influence between these protons and anyadded cations affects the equilibrium and hence the productdistribution. Cucurbit[n]urils where n>7 appears to be controlled by atemplating around a cation/anion cluster rather than a single ion, pair.Electrospray mass spectroscopy of larger cucurbiturils supports thisshowing multi charged cationic complexes.

Further influences upon the equilibrium and hence the product out comeis the precipitation of product complexes. For example increasing theconcentration by 10 times of a cation such as lithium in sulphuric acidchances the relative proportion of cucurbit[5]uril from 5% to 25% as aconsequence of the precipitation of the cucurbit[5]uril lithiumcomplexes.

In addition to equilibrium shifts caused by chances to the cationconcentration the equilibrium is also affected by the formation of thecucurbit[6]uril iodine complex which occurs under the reactionconditions where hydriodic acid is used and hydriodic acid decomposes toform iodine. The addition of red phosphorus eliminates this effect bythe in situ reduction of the iodine generated.

In addition, we have found that a wide range of other inorganic andorganic compounds can be used as templates. These affect the equilibriumthrough a variety of subtle effects including ion-dipole, diople-diopleand hydrogen bonding, hydrophobic and weak Van der Waals interactions.In essence, any material or compound stable to the reaction conditionscould act as a potential template.

INDUSTRIAL APPLICABILITY

The potential uses for cucurbit[n]urils are large with academic,industrial, analytical and pharmaceutical applications. As a class thesemolecules can be favourable compared to the cyclodextrins because bothmolecular systems posses a hydrophobic cavity with polar end caps.Cyclodextrins have been used in a wide range of applications includingslow release drugs, odour entrapment agents in plastic films, andenzimimics for synthesis. It is believed that cucurbit[n]urils will beof use in similar areas where benefit can be taken of the ability of thecucurbit[n]urils to take up molecules or compounds into there centralcavity. Such potential uses may include: Environmental (Water and Soil)

Remediation, by the binding of polluting products and their removal;

Preventative, eg, by binding of potential pollutants before wastes arereleased to the environment;

Uses in biodegradable polymers.

Domestic and Public

Incorporation into polymers as odourisers, releasing fragrances slowlyover time;

Or incorporated into polymers to trap unpleasant odours or toxic vapours

Encaptulation of bleaching and whitening agents.

Food

Flavour enhancers;

Flavour optimisers, hence hiding unpleasant flavours;

Polyphenol removal to reduce discolouration of juices.

Pharmaceutical

Slow release drugs, limiting side effects and reducing the frequency ofdoses;

Increasing drug stability in vivo or on the shelf;

Detoxification, for example, decreasing stomach irritations, or thetreatment of chemical allergens by encaptulation.

Agricultural/horticultural

Slow release of herbicides and pesticides;

Stabilisation of agricultural chemicals against light and heat.

Manufacturing

Enzyme/catalyst mimics;

Regioselective control over reaction products;

Manipulation of paint and polymer products;

Chromatographic columns for chemical purification;

Analytical tools and devices;

Printing and photography.

Miscellaneous

Volatility reduction, for storage, safety, or use;

Uses for insensitive munitions manufacture;

Forensic science.

Cucurbit[n]urils are thermally more robust than cyclodextrins and arestable to strong acid solutions unlike cyclodextrins.

The present inventors have also found that cucurbit[6]uril andcucurbit[7]uril can both bind dioxane aqueous solutions. This dioxanebinding properly can form the basis of processes for the removal ofdioxane. According to a further aspect of the present invention, thepresent invention provides a process for removing dioxane from a fluidcomprising contacting the fluid with cucurbit[6]uril and/orcucurbit[7]uril.

The physical removal of dioxane could take place using one of thefollowing techniques:

Cucurbit[6 or 7]uril bound to a non-reactive solid support (silica oralumina) where the dioxane would bind to the cucurbit[6 or 7]uril andthen be removed from solution by simple filtration to collect the solidsupport.

A solution of cucurbit[6 or 7]uril placed in dialysis tubing which wouldallow the passage of dioxane into the solution where it would be boundby the cucurbit[6 or 7]uril.

Incorporation of the cucurbit[6 or 7]uril into a solid clay support anduse filtration techniques to remove bound dioxane.

Incorporation into a polymer film. In this case the dioxane would beentrapped by the cucurbit[6 or 7]uril inside the polymer film. When thecapacity of the film has been reached it is simply removed from contactwith the product stream.

In all cases the material itself could be regenerated for repeated use.

If the dioxane is contained in the solid, for example indioxane/contaminated soil, the process of this aspect of the inventionmay comprise the further step of washing the soil with a fluid tothereby cause the dioxane to go into the fluid and subsequently treatingthe fluid in accordance with this aspect of the invention.

Cucurbit[5]uril has shown uptake of carbon monoxide. Accordingly, theinvention further provides a method for removing carbon monoxide from aliquid or vapour containing carbon monoxide by contacting the liquid orvapour with cucurbit[5]uril.

The present invention provides a method for producing a range ofcucurbit[n]urils and cucurbit[s,u]urils. The synthesis method results inthe production of a number of cucurbit[n]urils and cucurbit[s,u]urilsthat have never before been produced or isolated. Separation is possiblevia chromatography and/or selective precipitation. The productcucurbit[n]urils and cucurbit[s,u]urils are stable to vigorous reactionconditions over a wide range of pH values. They are soluble in aqueousacid or aqueous salt solutions. The method gives cucurbiturils in muchlarger yields than previously possible. The use of templating compoundsallows a degree of control over the relative amounts of the differentcucurbit[n]urils being produced.

Those skilled in the art will appreciate that the invention describedherein may be susceptible to variation and modifications other thanthose specifically described. It is to be understood that the presentinvention encompasses all such variations and modifications that fallwithin its spirit and scope.

What is claimed is:
 1. A method for producing a cucurbit[n]uril, where nis 4, 5, 6, 7, 8, 9, 10, 11 or 12, but excludingdecamethylcucurbit[5]uril and unsubstituted cucurbit[6]uril, comprisingmixing substituted and/or unsubstituted glycoluril with an acid and acompound that can form methylene bridges between glycoluril units, andheating the mixture to a temperature of from 20° to 120° C. to therebyform a cucurbit[n]uril.
 2. A method for producing a mixture of two ormore cucurbit[n]urils, where n is from 4 to 12, comprising mixingsubstituted and/or unsubstituted glycoluril with an acid and a compoundthat can form methylene bridges between glycoluril units, and heatingthe mixture to a temperature of from 20° to 120° C. to thereby form amixture of two or more cucurbit[n]urils.
 3. A method as claimed in claim2 wherein n is from 4 to
 10. 4. A method as claimed in claim 2 furthercomprising adding a templating compound to the mixture.
 5. A method asclaimed in claim 4 wherein said templating compound is selected fromammonium chloride, lithium chloride, sodium chloride, potassiumchloride, rubidium chloride, caesium chloride, ammonium chloride,lithium bromide, sodium bromide, potassium bromide, rubidium bromide,caesium bromide, lithium iodide, sodium iodide, potassium iodide,rubidium iodide, caesium iodide, potassium sulfate, lithium sulfate,tetrabutylammonium chloride, tetraethylammonium chloride, o-carborane,thioacetamide, N-(1-napthyl) ethylenediamine, 2,2′-biquinoline,p-bromoaniline, taurine, blue tetrazolium, 2-amino-3-methyl benzoicacid, indol-3-aldehyde, cysteine, 4-acetamidoaniline, p-aminophenol,acetamide, 4-aminoacetophenone, 4-dimethylaminobenzaldehyde,2-aminobenzimidazole, bis-(4,4′-bipyridyl)-α,α′-p-xylene, redphosphorus, and lithium p-toluenesulfonate.
 6. A method as claimed inclaim 4 wherein the templating compound is a salt.
 7. A method asclaimed in claim 6 wherein the anion of the salt corresponds to theanion of the acid in the mixture.
 8. A method as claimed in claim 4wherein two or more templating compounds are added to the mixture.
 9. Amethod as claimed in claim 2 wherein the acid comprises a strong mineralacid or a strong organic acid.
 10. A method as claimed in claim 2wherein the acid is selected from sulfuric acid, hydrochloric acid,hydrobromic acid, hydriodic acid, deuterated sulfuric acid, phosphoricacid, p-toluenesulfonic acid, and methane sulfonic acid.
 11. A method asclaimed in claim 2 further comprising adding a solvent to the reactionmixture.
 12. A method as claimed in claim 11 wherein the solvent isselected from trifluoroacetic acid, methanesulfonic acid and1,1,1-trifluoroethanol.
 13. A method as claimed in claim 2 wherein thecompound that can form methylene bridges between glycoluril unitscomprises formaldehyde, paraformaldehyde, trioxane or one or moreprecursors for formaldehyde.
 14. A method as claimed in claim 2 whereinthe mixture is heated to a temperature of from 20° C. to 110° C.
 15. Amethod as claimed in claim 14 wherein the mixture is heated to atemperature of from 60° to 110° C.
 16. A method as claimed in claim 14wherein the mixture is heated to a temperature of from 80° to 110° C.17. A method as claimed in claim 2, wherein the mixture is heated forbetween 1 hour and 24 hours.
 18. A method as claimed in claim 2 whereinthe acid has a concentration of at least 5 M.
 19. A method as claimed inclaim 2 wherein the mixture is allowed to stand at room temperatureuntil a gel is formed prior to heating.
 20. A method for producing asubstituted cucurbituril of the formula cucurbit[s,u]uril, wheres=number of substituted glycoluril units, u=number of unsubstitutedglycoluril units and s+u=4 to 12, but excludingdecamethylcucurbit[5]uril, comprising mixing substituted glycoluril andunsubstituted glycoluril with an acid and a compound that can formmethylene bridges between glycoluril units and heating the mixture to atemperature of from 20° to 120° C. to thereby form a cucurbit[s,u]uril.21. A method as claimed in claim 20 wherein the substituted glycolurichas a formula

wherein R₁ and R₂ are the same or different and are selected from anoptionally substituted straight chain, branched or cyclic, saturated orunsaturated hydrocarbon radical or a heterocyclyl radical or R₁ and R₂form a cyclic hydrocarbon radical.
 22. A method as claimed in claim 21wherein R₁ and R₂ are the same or different and are selected from alkyl,alkenyl, alkynyl, aryl and heterocyclyl radicals.
 23. A method asclaimed in claim 20 wherein s+u=4 to
 10. 24. A method as claimed inclaim 20 further comprising adding a templating compound to the mixture.25. A method as claimed in claim 24 wherein said templating compound isselected from ammonium chloride, lithium chloride, sodium chloride,potassium chloride, rubidium chloride, caesium chloride, ammoniumchloride, lithium bromide, sodium bromide, potassium bromide, rubidiumbromide, caesium bromide, lithium iodide, sodium iodide, potassiumiodide, rubidium iodide, caesium iodide, potassium sulfate, lithiumsulfate, tetrabutylammonium chloride, tetraethylammonium chloride,o-carborane, thioacetamide, N-(1-napthyl) ethylenediamine,2,2′-biquinoline, p-bromoaniline, taurine, blue tetrazolium,2-amino-3-methyl benzoic acid, indol-3-aldehyde, cysteine,4-acetamidoaniline, p-aminophenol, acetamide, 4-aminoacetophenone,4-dimethylaminobenzaldehyde, 2-aminobenzimidazole,bis-(4,4′-bipyridyl)-α,α′-p-xylene, red phosphorus, and lithiump-toluenesulfonate.
 26. A method as claimed in claim 24 where saidtemplating compound is a salt.
 27. A method as claimed in claim 26wherein the anion of the salt corresponds to the anion of the acid inthe mixture.
 28. A method as claimed in claim 24 wherein two or moretemplating compounds are added to the mixture.
 29. A method as claimedin claim 20 wherein the acid comprises a strong mineral acid or a strongorganic acid.
 30. A method as claimed in claim 20 wherein the acid isselected from sulfuric acid, hydrochloric acid, hydrobromic acid,hydroiodic acid, deuterated sulfuric acid, phosphoric acid,p-toluenesulfonic acid, and methane sulfonic acid.
 31. A method asclaimed in claim 20 further comprising adding a solvent to the mixture.32. A method as claimed in claim 31 wherein the solvent is selected fromtrifluoroacetic acid, methane sulfonic acid and 1,1,1-trifluoroethanol.33. A method as claimed in claim 20 wherein the compound that can formmethylene bridges between glycoluril units comprises formaldehyde,paraformaldehyde, trioxane or one or more precursors for formaldehyde.34. A method as claimed in claim 20 wherein the mixture is heated to atemperature of from 20° to 110° C.
 35. A method as claimed in claim 34wherein the mixture is heated to a temperature of from 60° to 110° C.36. A method as claimed in claim 34 wherein the mixture is heated to atemperature of from 80° to 110° C.
 37. A method as claimed in claim 20wherein the mixture is heated for between 1 hour and 24 hours.
 38. Amethod as claimed in claim 20 wherein the acid has a concentration of atleast 5M.
 39. A method as claimed in claim 20 wherein the mixture isallowed to stand at room temperature until a gel is formed prior toheating.
 40. A method for separating a mixture of cucurbit[n]urils,where n=4 to 12, by mixing the mixture of cucurbit[n]urils with a saltsolution, in which at least one of the cucurbit[n]urils, but not all ofthe cucurbit[n]urils, dissolves, and separating solids from thesolution.
 41. A method as claimed in claim 40 further comprisingrecovering at least one cucurbit[n]uril from the solids.
 42. A method asclaimed in claim 40 further comprising recovering at least onecucurbit[n]uril from solution.
 43. A method as claimed in claim 42further comprising passing the solution into contact with an ionexchange resin to thereby absorb dissolved cucurbit[n]urils onto theresin and subsequently eluting said cucurbit[n]urils from the resin. 44.A method for separating a mixture of cucurbit[n]urils, where n=4 to 10,by dissolving the mixture of cucurbit[n]urils and subjecting thethus-formed solution of cucurbit[n]urils to chromatographic separation.45. A method for separating a mixture of cucurbit[s,u]urils wheres=number of substituted glycoluril units, u=number of unsubstitutedglycoluril units and s+u=4 to 12 comprising dissolving the mixture ofcucurbit[s,u]urils and subjecting the thus-formed mixture ofcucurbit[s,u]urils to chromatographic separation.
 46. Cucurbit[n]uril,where n=4 to 12, excluding unsubstituted cucurbit[6]uril anddecamethylcucurbit[5]uril.
 47. Substituted cucurbiturils of the formulacucurbit[s,u]uril, wherein s=number of substituted glycoluril units andu=number of unsubstituted glycoluril units and s+u=4 to 12, butexcluding decamethylcucurbit[5]uril.
 48. A substituted glycoluril of theformula:


49. A substituted glycoluril of the formula:


50. A cucurbit[n]uril of the formula (I):

wherein n=4 to 12, and wherein, for each unit of the formula (II)

making up the cucurbit[n]uril, R₁ and R₂ are independently selected fromH, an optionally substituted straight chain, branched or cyclic,saturated or unsaturated hydrocarbon radical or a heterocyclyl radical,or R₁ and R₂ form a cyclic hydrocarbon radical, but excludingunsubstituted cucurbit[6]uril and decamethylcucurbit[5]uril.
 51. Acucurbit[n]uril according to claim 50 wherein for each unit of theformula (II) making up the cucurbit[n]uril, R₁ and R₂ are both H, and nis 4, 5, 7, 8, 9, 10, 11 or
 12. 52. A cucurbit[n]uril according to claim50, wherein for each unit of the formula (II) making up thecucurbituril, R₁ and R₂ are both H, or R₁ and R₂ are independentlyselected from an optionally substituted straight chain, branched orcyclic, saturated or unsaturated hydrocarbon radical or a heterocyclylradical, or R₁ and R₂ form a cyclic hydrocarbon radical.
 53. A methodfor producing a cucurbit[n]uril of the formula (I) as defined in claim50, but excluding unsubstituted cucurbit[6]uril anddecamethylcucurbit[5]uril, the method comprising mixing a glycoluril ofthe formula (III), or two or more glycolurils of the formula (III),

wherein R₁ and R₂ are independently selected from H, an optionallysubstituted straight chain, branched or cyclic, saturated or unsaturatedhydrocarbon radical or a heterocyclyl radical, or R₁ and R₂ form acyclic hydrocarbon radical, with an acid and a compound that can formmethylene bridges between glycoluril units, and heating the mixture to atemperature of from 20° to 120° C. to thereby form a cucurbit[n]uril offormula (I).
 54. A method as claimed in claim 53, wherein R₁ and R₂ arethe same or different and are selected from alkyl, alkenyl, alkynyl,aryl and heterocyclyl radicals.
 55. A method as claimed in claim 53,wherein R₁ and R₂ are H.
 56. A method as claimed in claim 53, whereinn=4 to
 10. 57. A method as claimed in claim 53, further comprisingadding a templating compound to the mixture.
 58. A method as claimed inclaim 57, wherein said templating compound is selected from ammoniumchloride, lithium chloride, sodium chloride, potassium chloride,rubidium chloride, caesium chloride, ammonium chloride, lithium bromide,sodium bromide, potassium bromide, rubidium bromide, caesium bromide,lithium iodide, sodium iodide, potassium iodide, rubidium iodide,caesium iodide, potassium sulfate, lithium sulfate, tetrabutylammoniumchloride, tetraethylammonium chloride, o-carborane, thioacetamide,N-(1-napthyl) ethylenediamine, 2,2′-biquinoline, p-bromoaniline,taurine, blue tetrazolium, 2-amino-3-methyl benzoic acid,indol-3-aldehyde, cysteine, 4-acetamidoaniline, p-aminophenol,acetamide, 4-aminoacetophenone, 4-dimethylaminobenzaldehyde,2-aminobenzimidazole, bis-(4,4′-bipyridyl)-α,α′-p-xylene, redphosphorus, and lithium p-toluenesulfonate.
 59. A method as claimed inclaim 57 wherein said templating compound is a salt.
 60. A method asclaimed in claim 59 wherein the anion of the salt corresponds to theanion of the acid in the mixture.
 61. A method as claimed in claim 57wherein two or more templating compounds are added to the mixture.
 62. Amethod as claimed in claim 53 wherein the acid comprises a strongmineral acid or a strong organic acid.
 63. A method as claimed in claim53 wherein the acid is selected from sulfuric acid, hydrochloric acid,hydrobromic acid, hydriodic acid, deuterated sulfuric acid, phosphoricacid, p-toluenesulfonic acid, and methane sulfonic acid.
 64. A method asclaimed in claim 53 further comprising adding a solvent to the mixture.65. A method as claimed in claim 64 wherein the solvent is selected fromtrifluoroacetic acid, methane sulfonic acid and 1,1,1-trifluoroethanol.66. A method as claimed in claim 53 wherein the compound that can formmethylene bridges between glycoluril units comprises formaldehyde,paraformaldehyde, trioxane or one or more precursors for formaldehyde.67. A method as claimed in claim 53 wherein the mixture is heated to atemperature of from 20° to 110° C.
 68. A method as claimed in claim 67wherein the mixture is heated to a temperature of from 60° to 110° C.69. A method as claimed in claim 67 wherein the mixture is heated to atemperature of from 80° to 110° C.
 70. A method as claimed in claim 53wherein the mixture is heated for between 1 hour and 24 hours.
 71. Amethod for producing a cucurbit[n]uril, where n is 4 to 12, comprisingmixing a diether of formula 2, or two or more diethers of the formula 2,

wherein R₁ and R₂ are independently selected from H, an optionallysubstituted straight chain, branched or cyclic, saturated or unsaturatedhydrocarbon radical or a heterocyclyl radical, or R₁ and R₂ form acyclic hydrocarbon radical, and optionally a glycoluril of formula (III)or two or more glycolurils of the formula (III)

wherein R₁ and R₂ are independently selected from H, an optionallysubstituted straight chain, branched or cyclic, saturated or unsaturatedhydrocarbon radical or a heterocyclyl radical, or R₁ and R₂ form acyclic hydrocarbon radical, with an acid, and heating the mixture to atemperature of from 20° to 120° C. to thereby form a cucurbit[n]uril.72. A method as claimed in claim 71 wherein the mixture is heated to atemperature of from 20° to 110° C.
 73. A method as claimed in claim 72wherein the mixture is heated to a temperature of from 60° to 110° C.74. A method as claimed in claim 72 wherein the mixture is heated to atemperature of from 80° to 110° C.
 75. A method as claimed in claim 71wherein R₁ and R₂ are selected from alkyl, alkenyl, alkynyl, aryl andheterocyclyl radicals.
 76. A method as claimed in claim 71 wherein R₁and R₂ are H.
 77. A method as claimed in claim 71 wherein n=4 to
 10. 78.A method as claimed in claim 71 further comprising adding a templatingcompound to the mixture.
 79. A method as claimed in claim 78 whereinsaid templating compound is selected from ammonium chloride, lithiumchloride, sodium chloride, potassium chloride, rubidium chloride,caesium chloride, ammonium chloride, lithium bromide, sodium bromide,potassium bromide, rubidium bromide, caesium bromide, lithium iodide,sodium iodide, potassium iodide, rubidium iodide, caesium iodide,potassium sulfate, lithium sulfate, tetrabutylammonium chloride,tetraethylammonium chloride, o-carborane, thioacetamide, N-(1-napthyl)ethylenediamine, 2,2′-biquinoline, p-bromoaniline, taurine, bluetetrazolium, 2-amino-3-methyl benzoic acid, indol-3-aldehyde, cysteine,4-acetamidoaniline, p-aminophenol, acetamide, 4-aminoacetophenone,4-dimethylaminobenzaldehyde, 2-aminobenzimidazole,bis-(4,4′-bipyridyl)-α,α′-p-xylene, red phosphorus, and lithiump-toluenesulfonate.
 80. A method as claimed in claim 78 wherein saidtemplating compound is a salt.
 81. A method as claimed in claim 80wherein the anion of the salt corresponds to the anion of the acid inthe mixture.
 82. A method as claimed in claim 78 wherein two or moretemplating compounds are added to the mixture.
 83. A method as claimedin claim 71 wherein the acid comprises a strong mineral acid or a strongorganic acid.
 84. A method as claimed in claim 71 wherein the acid isselected from sulfuric acid, hydrochloric acid, hydrobromic acid,hydriodic acid, deuterated sulfuric acid, phosphoric acid,p-toluenesulfonic acid, and methane sulfonic acid.
 85. A method asclaimed in claim 71 further comprising adding a solvent to the mixture.86. A method as claimed in claim 85 wherein the solvent is selected fromtrifluoroacetic acid, methane sulfonic acid and 1,1,1-trifluoroethanol.87. A method as claimed in claim 71 wherein the mixture is heated forbetween 1 hour and 24 hours.
 88. A method for producing acucurbit[n]uril, where n=4 to 12, comprising mixing a tetrol of theformula 1, or two or more tetrols of the formula 1,

wherein R₁ and R₂ are independently selected from H, an optionallysubstituted straight chain, branched or cyclic, saturated or unsaturatedhydrocarbon radical or a heterocyclyl radical, or R₁ and R₂ form acyclic hydrocarbon radical, with an acid, and heating the mixture to atemperature of from 20° to 120° C. to thereby form a cucurbit[n]uril.89. A method as claimed in claim 88 wherein the mixture is heated to atemperature of from 20° to 110° C.
 90. A method as claimed in claim 89wherein the mixture is heated to temperature of from 60° to 110° C. 91.A method as claimed in claim 89 wherein the mixture is heated to atemperature of from 80° to 110° C.
 92. A method as claimed in claim 88wherein R₁ and R₂ are selected from alkyl, alkenyl, alkynyl, aryl andheterocyclyl radicals.
 93. A method as claimed in claim 88 wherein R₁and R₂ are H.
 94. A method as claimed in claim 88 wherein n=4 to
 10. 95.A method as claimed in claim 88 further comprising adding a templatingcompound to the mixture.
 96. A method as claimed in claim 95 whereinsaid templating compound is selected from ammonium chloride, lithiumchloride, sodium chloride, potassium chloride, rubidium chloride,caesium chloride, ammonium chloride, lithium bromide, sodium bromide,potassium bromide, rubidium bromide, caesium bromide, lithium iodide,sodium iodide, potassium iodide, acbidium iodide, caesium iodide,potassium sulfate, lithium sulfate, tetrabutylammonium chloride,tetraethylammonium chloride, o-carborane, thioacetamide, N-(1-napthyl)ethylenediamine, 2,2′-biquinoline, p-bromoaniline, taurine, bluetetrazolium, 2-amino-3-methyl benzoic acid, indol-3-aldehyde, cysteine,4-acetamidoaniline, p-aminophenol, acetamide, 4-aminoacetophenone,4-dimethylaminobenzaldehyde, 2-aminobenzimidazole,bis-(4,4′-bipyridyl)-α,α′-p-xylene, red phosphorus, and lithiump-toluenesulfonate.
 97. A method as claimed in claim 95 wherein saidtemplating compound is a salt.
 98. A method as claimed in claim 97wherein the anion of the salt corresponds to the anion of the acid inthe mixture.
 99. A method as claimed in claim 95 wherein two or moretemplating compounds are added to the mixture.
 100. A method as claimedin claim 88 wherein the acid comprises a strong mineral acid or a strongorganic acid.
 101. A method as claimed in claim 88 wherein the acid isselected from sulfuric acid, hydrochloric acid, hydrobromic acid,hydriodic acid, deuterated sulfuric acid, phosphoric acid,p-toluenesulfonic acid, and methane sulfonic acid.
 102. A method asclaimed in claim 88 further comprising adding a solvent to the mixture.103. A method as claimed in claim 102 wherein the solvent is selectedfrom trifluoroacetic acid, methane sulfonic acid and1,1,1-trifluoroethanol.
 104. A method as claimed in claim 88 wherein themixture is heated for between 1 hour and 24 hours.